OBJECTIVE

Highly stable, submicron lactate dehydrogenase (LDH) and lysozyme particles may be produced by thin film freezing (TFF) of aqueous solutions followed by lyophilization.

METHODS

The LDH activity was determined by measuring the decrease in absorbance of NADH over time for the reaction of pyruvate to lactate. For lysozyme the particle morphology was determined by scanning electron microscopy (SEM) and compared with the specific surface area (BET) and the particle size, as measured by laser light scattering,

RESULTS

Protein particles with an average diameter of 300 nm and 100% enzyme activity upon reconstitution (for LDH) were formed by TFF. Droplets of protein solutions, 3.6 mm in diameter, spread upon impact with 223 and 133 K metal surfaces to form cylindrical disks with thicknesses of 200-300 microm. Calculated cooling rates of the disks of 10(2) K/s were confirmed experimentally with infrared measurements.

CONCLUSIONS

The cooling rates of 10(2) K/s, intermediate to those in lyophilization (1 K/min) and spray freeze-drying (SFD) (10(6) K/s), were sufficiently fast to produce sub-micron protein particles with surface areas of 31-73 m2/g, an order of magnitude higher than in lyophilization. In addition, the low surface area/volume ratio (32-45 cm(-1)) of the gas-liquid interface led to minimal protein adsorption and denaturation relative to SFD.

BACKGROUND

Shenfu decoction (SFD) is a water extract of the dried root or root stalk of Panax ginseng C. A. Mey (Asian ginseng) and the lateral root of Aconitum carmichaeli Debx (prepared by Fuzi, Heishunpian in Chinese). It has been used to treat heart failure for over a thousand years. The main active components of SFD, ginsenosides and higenamine, enhance heart contractility, increase the coronary blood supply, improve ischemic myocardial metabolism, scavenge free radicals and protect myocardial ultrastructure.

OBJECTIVE

To investigate the effect of SFD on quality of life (QOL) and hepatic function in symptomatic chronic heart failure (CHF) patients.

METHODS

Forty patients enrolled in the study were randomized into two groups: an SFD group (18 cases) and a control group (22 cases). All the patients received standard heart failure therapy, and the SFD group patients were also treated with Shenfu granules for 14 days as an adjunctive therapy. The effects of SFD on QOL, plasma alanine aminotransferase (ALT) level, cardiac function, left ventricular ejection fraction (LVEF) and tumor necrosis factor-α (TNF-α) level were studied. ALT threshold in hepatic injury are 21U/L for men and 17U/L for women.

RESULTS

Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores were improved by 35.27±10.72 vs. 23.87±11.96 in the SFD and control groups respectively (p<0.01). Subgroup analysis of the MLHFQ results demonstrated that both physical and emotional scores were significantly higher in the SFD group (21.00±5.66 vs. 16.75±6.25, p<0.05; 4.64±4.84 vs. 1.13±2.85, p<0.05). Circulating ALT was significantly decreased by SFD (13.3IU/L vs. 0.6IU/L, p<0.01). The grading of cardiac function and LVEF were increased by 1.6±0.5 vs. 1.1±0.3 and 18%±13% vs. 8%±8% in the SFD and control groups respectively (p<0.05 and p<0.05). The level of TNF-α declined more in SFD than control group (64.8±5.0 to 57.6±4.1, p<0.05; vs. 61.6±5.9 vs. 57.7±3.2. p>0.05).

CONCLUSIONS

Compared with standard heart failure treatment, oral SFD as an adjuvant therapy significantly improved QOL and hepatic injury in CHF patients.

Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are a major cause of vision loss. However, the mechanisms underlying their progression remain ill-defined. This is partly due to the lack of disease models recapitulating the human pathology. Furthermore, in vivo studies have yielded limited understanding of the role of specific cell types in the eye vs. systemic influences (e.g., serum) on the disease pathology. Here, we use human induced pluripotent stem cell-retinal pigment epithelium (hiPSC-RPE) derived from patients with three dominant MDs, Sorsby's fundus dystrophy (SFD), Doyne honeycomb retinal dystrophy/malattia Leventinese (DHRD), and autosomal dominant radial drusen (ADRD), and demonstrate that dysfunction of RPE cells alone is sufficient for the initiation of sub-RPE lipoproteinaceous deposit (drusen) formation and extracellular matrix (ECM) alteration in these diseases. Consistent with clinical studies, sub-RPE basal deposits were present beneath both control (unaffected) and patient hiPSC-RPE cells. Importantly basal deposits in patient hiPSC-RPE cultures were more abundant and displayed a lipid- and protein-rich "drusen-like" composition. Furthermore, increased accumulation of COL4 was observed in ECM isolated from control vs. patient hiPSC-RPE cultures. Interestingly, RPE-specific up-regulation in the expression of several complement genes was also seen in patient hiPSC-RPE cultures of all three MDs (SFD, DHRD, and ADRD). Finally, although serum exposure was not necessary for drusen formation, COL4 accumulation in ECM, and complement pathway gene alteration, it impacted the composition of drusen-like deposits in patient hiPSC-RPE cultures. Together, the drusen model(s) of MDs described here provide fundamental insights into the unique biology of maculopathies affecting the RPE-ECM interface.

OBJECTIVE

The use of small photon fields is now an established practice in stereotactic radiosurgery and radiotherapy. However, due to a lack of lateral electron equilibrium and high dose gradients, it is difficult to accurately measure the dosimetric quantities required for the commissioning of such systems. Moreover, there is still no metrological dosimetric reference for this kind of beam today. In this context, the first objective of this work was to determine and to compare small fields output factors (OF) measured with different types of active detectors and passive dosimeters for three types of facilities: a CyberKnife(®) system, a dedicated medical linear accelerator (Novalis) equipped with m3 microMLC and circular cones, and an adaptive medical linear accelerator (Clinac 2100) equipped with an additional m3 microMLC. The second one was to determine the kQclin,Qmsr (fclin,fmsr) correction factors introduced in a recently proposed small field dosimetry formalism for different active detectors.

METHODS

Small field sizes were defined either by microMLC down to 6 × 6 mm(2) or by circular cones down to 4 mm in diameter. OF measurements were performed with several commercially available active detectors dedicated to measurements in small fields (high resolution diodes: IBA SFD, Sun Nuclear EDGE, PTW 60016, PTW 60017; ionizing chambers: PTW 31014 PinPoint chamber, PTW 31018 microLion liquid chamber, and PTW 60003 natural diamond). Two types of passive dosimeters were used: LiF microcubes and EBT2 radiochromic films.

RESULTS

Significant differences between the results obtained by several dosimetric systems were observed, particularly for the smallest field size for which the difference in the measured OF reaches more than 20%. For passive dosimeters, an excellent agreement was observed (better than 2%) between EBT2 and LiF microcubes for all OF measurements. Moreover, it has been shown that these passive dosimeters do not require correction factors and can then be used as reference dosimeters. Correction factors for the active detectors have then been determined from the mean experimental OF measured by the passive dosimeters.

CONCLUSIONS

Four sets of correction factors needed to apply the new small field dosimetry formalism are provided for several active detectors. A protocol for small photon beams OF determination based on passive dosimeters measurements has been recently proposed to French radiotherapy treatment centers.

Although eye movements during reading are modulated by cognitive processing demands, they also reflect visual sampling of the input, and possibly preparation of output for speech or the inner voice. By simultaneously recording eye movements and the voice during reading aloud, we obtained an output measure that constrains the length of time spent on cognitive processing. Here we investigate the dynamics of the eye-voice span (EVS), the distance between eye and voice. We show that the EVS is regulated immediately during fixation of a word by either increasing fixation duration or programming a regressive eye movement against the reading direction. EVS size at the beginning of a fixation was positively correlated with the likelihood of regressions and refixations. Regression probability was further increased if the EVS was still large at the end of a fixation: if adjustment of fixation duration did not sufficiently reduce the EVS during a fixation, then a regression rather than a refixation followed with high probability. We further show that the EVS can help understand cognitive influences on fixation duration during reading: in mixed model analyses, the EVS was a stronger predictor of fixation durations than either word frequency or word length. The EVS modulated the influence of several other predictors on single fixation durations (SFDs). For example, word-N frequency effects were larger with a large EVS, especially when word N-1 frequency was low. Finally, a comparison of SFDs during oral and silent reading showed that reading is governed by similar principles in both reading modes, although EVS maintenance and articulatory processing also cause some differences. In summary, the EVS is regulated by adjusting fixation duration and/or by programming a regressive eye movement when the EVS gets too large. Overall, the EVS appears to be directly related to updating of the working memory buffer during reading.

Twenty new cases of Silo filler's disease (SFD) have been collected, documenting the incidence and clinical features of exposure to nitrogen oxides present in freshly filled silos. Cases of SFD were identified using a statewide computerized discharge diagnosis system. Fifteen of these were identified in the index period, allowing us to calculate an approximate annual incidence of 5.0 cases/100,000 silo-associated farm workers/yr in New York State. All cases occurred during harvest periods, with 80% in September and October. Corn silage was the gas source in 18 (90%). All cases involved young white men (mean age, 31.5 yr). The most common presenting feature was dyspnea. All victims entered a silo during the peak danger period, and only one used recommended ventilation techniques. Four cases ended in death (20% mortality). Silo filler's disease, although rare, is a potentially devastating disease involving otherwise young, healthy farm workers. It is readily prevented.

Pulmonary delivery of messenger RNA (mRNA) has considerable potential as therapy or vaccine for a range of lung diseases. Inhaled dry powder formulation of mRNA is particularly attractive as it has superior stability and dry powder inhaler is relatively easy to use. A safe and effective mRNA delivery vector as well as a suitable particle engineering method are required to produce a dry powder formulation that is respirable and mediates robust transfection in the lung. Here, we introduce a novel RNA delivery vector, PEG₁₂KL4, in which the synthetic cationic KL4 peptide is attached to a monodisperse linear PEG of 12-mers. The PEG₁₂KL4 formed nano-sized complexes with mRNA at 10:1 ratio (w/w) and mediated effective transfection on human lung epithelial cells. PEG₁₂KL4/mRNA complexes were successfully formulated into dry powder by spray drying (SD) and spray freeze drying (SFD) techniques. Both SD and SFD powder exhibited satisfactory aerosol properties for inhalation. More importantly, the biological activity of the PEG₁₂KL4 /mRNA complexes were successfully preserved after drying. Using luciferase mRNA, the intratracheal administration of the liquid or powder aerosol of PEG₁₂KL4 /mRNA complexes at a dose of 5 µg mRNA resulted in luciferase expression in the deep lung region of mice 24 h post-transfection. The transfection efficiency was superior to naked mRNA or lipoplexes (Lipofectamine 2000), in which luciferase expression was weaker and restricted to the tracheal region only. There was no sign of inflammatory response or toxicity of the PEG₁₂KL4 /mRNA complexes after single intratracheal administration. Overall, PEG₁₂KL4 is an excellent mRNA transfection agent for pulmonary delivery. This is also the first study that successfully demonstrates the preparation of inhalable dry powder mRNA formulations with in vivo transfection efficiency, showing the great promise of PEG₁₂KL4 peptide as a mRNA delivery vector candidate for clinical applications.

Idiopathic environmental intolerance (IEI) refers to a polysymptomatic condition, similar to somatoform disorders. Various processes seem to contribute to its yet unknown etiology. Attention and memory for somatic symptom and IEI-trigger words was compared among participants with IEI (n = 54), somatoform disorders (SFD; n = 44) and control participants (n = 54). Groups did not differ in a dot-probe task. However, in an emotional Stroop task, attention was biased in IEI and SFD groups toward symptom words but not toward IEI-trigger words. Only the IEI group rated trigger words as more unpleasant and more arousing, and participants remembered them better in a recognition task. These implicit and explicit cognitive abnormalities in IEI and SFD may maintain processes of somatosensory amplification.

BACKGROUND

To compare the efficacy of pregabalin and gabapentin at comparable effective dose levels in patients with refractory partial epilepsy.

METHODS

Eight randomized placebo controlled trials investigating the efficacy of pregabalin (4 studies) and gabapentin (4 studies) over 12 weeks were identified with a systematic literature search. The endpoints of interest were "responder rate" (where response was defined as at least a 50% reduction from baseline in the number of seizures) and "change from baseline in seizure-free days over the last 28 days (SFD)". Results of all trials were analyzed using an indirect comparison approach with placebo as the common comparator. The base-case analysis used the intention-to-treat last observation carried forward method. Two sensitivity analyses were conducted among completer and responder populations.

RESULTS

The base-case analysis revealed statistically significant differences in response rate in favor of pregabalin 300 mg versus gabapentin 1200 mg (odds ratio, 1.82; 95% confidence interval, 1.02, 3.25) and pregabalin 600 mg versus gabapentin 1800 mg (odds ratio, 2.52; 95% confidence interval, 1.21, 5.27). Both sensitivity analyses supported the findings of the base-case analysis, although statistical significance was not demonstrated. All dose levels of pregabalin (150 mg to 600 mg) were more efficacious than corresponding dosages of gabapentin (900 mg to 2400 mg) in terms of SFD over the last 28 days.

CONCLUSIONS

In patients with refractory partial epilepsy, pregabalin is likely to be more effective than gabapentin at comparable effective doses, based on clinical response and the number of SFD.

Early intervention with budesonide is an effective strategy for mild persistent asthma, which has been shown to provide additional clinical benefits at a low incremental cost using USA cost data. The present authors analysed whether this strategy would be cost-effective using cost data for other countries. Based on the 3-yr prospective, randomised, double-blind inhaled Steroid Treatment As Regular Therapy (START) in early asthma study (comparing budesonide and placebo combined with usual asthma therapy), the cost-effectiveness was estimated separately for eight different countries, from both healthcare payer and societal perspectives, of adding budesonide to usual asthma therapy. Local unit costs were applied to data for the total trial population. Incremental cost-effectiveness ratios (ICER) were estimated as cost per symptom-free day (SFD) gained. Budesonide increased SFDs by an average of 14.1 days annually. From a healthcare payer perspective, budesonide would reduce the total cost of asthma care in Australia. In Sweden, Canada, France, Spain, UK, China and the USA, the ICER ranged from US$2.4-11.3 per SFD. From a societal perspective, budesonide would be cost-saving in Australia, Canada and Sweden. In conclusion, for countries where costs with budesonide are higher, the policy implication has to be determined by that health system's willingness to pay for an additional symptom-free day. However, where budesonide therapy increases symptom-free days and reduces total costs, the policy conclusion clearly favours early intervention.

BACKGROUND

Sorsby's fundus dystrophy (SFD) and age related macular degeneration (ARMD) are retinal diseases associated with a high level of accumulation of mutant and wild type TIMP-3, respectively, in Bruch's membrane. The pathogenic role of TIMP-3 in these diseases is uncertain, but causative mutations have been identified in the TIMP-3 gene of patients with SFD. Recent reports that TIMP-3 causes apoptosis in certain cell types and not in others prompted the authors to investigate whether TIMP-3 causes apoptosis in cultured retinal pigment epithelium (RPE) cells.

METHODS

RPE and MCF-7 cells (as a positive control) were initially infected with replication deficient adenovirus, to overexpress beta-galactosidase (RAdLacZ) or TIMP-3 (RAdTIMP-3). TIMP-3 was detected by western blotting and ELISA. Cell viability was defined by cell counts. ISEL was used to investigate the mechanism of cell death.

RESULTS

Cultured RPE cells produced small quantities of endogenous TIMP-3 and remained viable. However, overexpression of TIMP-3 caused a dose related death of RPE cells. The mechanism of cell death was apoptosis.

CONCLUSIONS

The previously unreported finding of TIMP-3 induced apoptosis of RPE cells may account for some of the early features seen in SFD and ARMD.

OBJECTIVE

To estimate the cost effectiveness of different classes of antidepressants in the UK National Health Service. DESIGN, PATIENTS AND INTERVENTIONS: The use of the serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) venlafaxine was compared with that of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in patients with major depressive disorder (MDD). A meta-analysis determined the clinical success rate, and a decision tree was constructed by interviewing general practitioners and psychiatrists. Adding pharmacological and nonpharmacological treatment costs, meta-analytic rates were applied to the decision tree to calculate the expected cost and outcome for each drug. Cost effectiveness was determined using a composite measure of outcome [symptom-free days (SFD)].

RESULTS

The meta-analysis included data from 44 studies on 4033 patients. The highest overall efficacy rate for outpatients with MDD was with venlafaxine use (73.7%), compared with 61.4% for SSRIs and 59.3% for TCAs. Treatment with venlafaxine yielded the lowest outpatient cost for a SFD (10.53 Pounds), compared with 13.23 Pounds for SSRIs and 15.52 Pounds for TCAs (1998 values).

CONCLUSIONS

Using this economic model, venlafaxine appears to be a cost-effective treatment for outpatients with MDD in the UK.

Spray-freeze-drying (SFD) of oleanolic acid (OA), a BCS Class IV compound, with polyvinylpyrrolidone-40 (PVP-40) as stabilizer and sodium caprate (SC) as wetting agent and penetration enhancer produced kinetically stable, amorphous solid dispersion systems with superior in vitro dissolution performance, and better and more uniform absorption in comparison with commercial OA tablet. Relative to the SC-free formulation, the presence of SC in the formulation resulted in a significant increase in the in vivo absorption rate of OA while exerting no apparent impact on the extent of OA absorption. The SFD-processed OA formulations and commercial OA tablet generally exhibited large inter-animal variability in oral bioavailability, consistent with the absorption characteristics of BCS Class IV compounds. Inclusion of SC coupled with the replacement of OA with its sodium salt (OA-Na) in the formulation was shown to substantially decrease the observed absorption variability. Above results suggested that increases in both dissolution rate and intestinal permeability of BCS Class IV compounds, as exemplified by the SFD-processed dispersion system containing both OA-Na and SC, are critical to reducing the large inter-individual absorption variability commonly observed with this class of drugs.

Cutaneous tuberculosis continues to be a significant medical problem even with the advent of highly effective antituberculous drugs. It constitutes about 1.5% of all extra pulmonary tuberculosis. The prevalence in children varies from 18 to 54% in India. There is no gender predilection and the infection occurs with increased frequency in 10-14 year age group. Intrafamilial source of TB has been observed very frequently. A concomitant TB lymphadenitis is most common while involvement of other systemic organs like lung, bone and abdomen has also been observed. Protective efficacy of BCG is debatable and not yet fully defined. Of all the clinical types, scrofuloderma (SFD) is the most commonly encountered variant followed by lupus vulgaris (LV) and tuberculosis verrucosa cutis (TBVC). Lichen scrofulosorum (LS) is generally found to be associated with systemic TB focus in about 72% of cases. The impact of HIV on childhood cutaneous TB seems to be minimal. Similar to adults, the diagnosis of cutaneous tuberculosis relies mainly on histopathology, culture on LJ medium or radiometric BACTEC 460 TB culture system and PCR. In addition Mantoux positivity and a positive therapeutic trial with anti-tubercular drugs may be a good pointer to tubercular infection. A thorough clinical evaluation and exhaustive investigations to pin-point associated systemic focus is advocated as the latter has an impact on the duration of treatment. Cutaneous TB in children is treated as per the recommendations of therapy for extrapulmonary TB.

IGF-II associates with feto-placental growth in rodent and human. We determined three tag-single nucleotide polymorphisms (SNPs) to investigate haplotype frequency of IGF2 relative to size at birth in 134 healthy Japanese infants. In addition, a total of 276 healthy infants were investigated to determine whether common genetic variation of IGF2 might contribute to feto-placental growth using haplotype analysis. Further, quantitative methylation analysis of the IGF2/H19 was performed using the MassARRAY Compact system. In the initial study, the frequency of haplotype CTG from the paternal allele in small for date (SFD) infants was significantly higher than that in non-SFD infants (p = 0.03). In a second study, the CTG haplotype infants exhibited significantly lower birth length, weight, and placental weight compared with non-CTG infants. Further, the number of infants less than -1.5 SD (SD) birth weight in CTG haplotype was higher than those in non-CTG infants. There was no significant difference in the methylation status of H19/IGF2 in the two haplotypes. In conclusion, inheriting the IGF2 CTG haplotype from a paternal allele results in reduced feto-placental growth, but it is not associated with the methylation status of IGF2/H19.

A unique size-dependent strain hardening mechanism, that achieves both high strength and ductility, is demonstrated for penta-twinned Ag nanowires (NWs) through a combined experimental-computational approach. Thin Ag NWs are found to deform via the surface nucleation of stacking fault decahedrons (SFDs) in multiple plastic zones distributed along the NW. Twin boundaries lead to the formation of SFD chains that locally harden the NW and promote subsequent nucleation of SFDs at other locations. Due to surface undulations, chain reactions of SFD arrays are activated at stress concentrations and terminated as local stress decreases, revealing insensitivity to defects imparted by the twin structures. Thick NWs exhibit lower flow stress and number of distributed plastic zones due to the onset of necking accompanied by more complex dislocation structures.

OBJECTIVE

To describe the phenotype and genotype of a family with suspected Sorsby fundus dystrophy (SFD).

METHODS

Case reports and results of deoxyribonucleic acid (DNA) analysis.

METHODS

Clinical features were determined by complete ophthalmologic examination or by review of medical records. Mutational analysis of the tissue inhibitor of metalloproteinase (TIMP)3 gene was performed by DNA resequencing. Biochemical properties of the mutant TIMP3 protein were studied, and phylogenetic and molecular modeling analyses of TIMP proteins were performed.

RESULTS

Fundi of four affected family members demonstrated active or regressed bilateral choroidal neovascularization, whereas another affected individual displayed severe diffuse pigmentary degeneration associated with nyctalopia characteristic of SFD. Onset of disease occurred in the fifth to seventh decades of life. A heterozygous His158Arg mutation was found in seven affected family members and was absent from an unaffected member and 98 unrelated controls. Bioinformatic analyses indicate that histidine 158 is an evolutionarily conserved residue in most vertebrate TIMP homologs and predict that substitution by arginine disrupts TIMP3 function. The mutant protein appears to be expressed by fibroblasts from an affected family member. Molecular modeling suggests that TIMP3 residue 158 may be part of a protein-protein interaction interface.

CONCLUSIONS

A novel mutation in TIMP3 causes a late-onset form of SFD in this family. His158Arg is the first reported TIMP3 SFD coding sequence mutation that does not create an unpaired cysteine. Further study of this unusual mutation may provide insight into the mechanism of SFD pathogenesis.

Shenfu decoction (SFD) is a well-known important traditional Chinese medicine prescription that has been used to treat chronic heart failure (CHF) for many years in China. However, its holistic therapeutic effects and mechanism are not yet well understood. Here, a UPLC/TOF-MS-based metabonomic study was conducted to explore potential biomarkers to increase the understanding of CHF and to assess the integral efficacy of SFD for CHF in rats. Principal component analysis was used to investigate the global metabonomic alterations and to evaluate the therapeutic effects of SFD in rats. Clear separations were observed not only in the comparison of dynamic trajectories but also in the comparison of the metabolite profiles of the normal controls, the model group (CHF), the sham surgery group and the SFD-treated group. The results indicated that SFD exerted therapeutic efficacies for CHF, which were in accordance with the results of the echocardiographic and haemodynamic assay. Furthermore, 16 potential biomarkers from urine samples and 13 potential biomarkers from serum samples of CHF rats were identified and were mainly related to inflammation and to dysfunction of amino acids and energy metabolism. The therapeutic effects of SFD on CHF were partially due to the restoration of these disturbed pathways. This study provides a useful approach for exploring the mechanism of myocardial infarction (MI)-induced CHF and for evaluating the efficacy of SFD on CHF.

OBJECTIVE

To correlate quantitative analysis of ultrasonographic images of normal (injury-free) equine superficial digital flexor (SDF) tendons and equine SFD tendons that have pathologic changes with corresponding histologic sections.

METHODS

4 SDF tendons, 2 of which had various stages of tissue integrity. The 2 ipsilateral tendons were used as points of reference.

METHODS

Tendons were mounted in a custom-made device that permitted sequential scanning, transversely and perpendicular to the tendon long axis. At precise steps of 0.5 mm, transverse ultrasonographic images were collected. Subsequently, tendons were fixed and prepared for histologic examination. The following 8 tissue types were discerned: normal young, normal old, necrotic, early granulation, late granulation, early fibrotic, late fibrotic, and scar tissues. In areas of interest, the corresponding ultrasonographic images were selected for gray level statistical analysis.

RESULTS

Compared with other tissue types, early-stage granulation tissue was characterized by substantially lower mean gray level and a clearly different histogram. Necrotic tissue had a higher mean gray level, with a virtually normal histogram. In late granulation and early fibrotic tissues, the mean gray level and the histogram could not be discerned from those of normal tendon tissue. The same applied to late fibrotic and scar tissues; mean gray levels were fractionally lower than those of normal tendon tissue with a completely normal histogram.

CONCLUSIONS

Although quantification of the transverse ultrasonographic image by use of first-order gray level statistics may be helpful, the method is not sufficiently sensitive to accurately and unequivocally determine the type of tendon tissue. Quantitative analysis should incorporate transverse and longitudinal information.

OBJECTIVE

To find the incidence of fetal complications in Indian diabetic mothers with tight glycaemic control (TC), its comparison with other levels of glycaemic control, i.e., acceptable control (AC), uncontrolled (UC), and relevant international data.

METHODS

A total of 240 mothers with diabetes mellitus (DM) and pregnancy were risk-matched and selected from the Antenatal Clinic of NRS Medical College, 176 of whom had gestational diabetes mellitus (GDM) and 64 had pregestational diabetes mellitus (PGDM), and were put on exercise, diet and or insulin therapy. Glycaemic parameters monitored include fasting plasma glucose (FPG), 2 hr. postprandial plasma glucose (PPPG) and HbA1C. TC had - FPG < 70 mg/dl, PPPG < 100 mg/dl, HBA1C < 6.5%; AC with FPG 70-95 mg/dl, 2 hr. PPPG 100-120, HBA1C 6.5-7.5% and UC had FPG>> 95 mg/ dl, 2 hr. PPPG>> 120 mg/dl and HBA1C>> 7.5%. Fetal parameters monitored included large-for-date babies (LGA), small-for-date babies (SFD), birth asphyxia, perinatal death, neonatal hypoglycemia, neonatal hypocalcaemia and congenital anomalies.

RESULTS

(i) LGA-AC had the best results (0% vs. 12.5 and 22.29%); (ii) SFD-TC and AC had worst results (16.7% and 18.18% vs. 0%); (iii) Birth asphyxia-AC fared worse 18.18% vs. 4.16% and 0%; (iv) perinatal death and congenital anomalies showed significant reduction with tight control (4.16% and 0% respectively); (v) Neonatal hypoglycemia is lowered in TC compared with UC while neonatal hypocalcaemia does not show any alteration. For PGDM patients there is little intra-group variability of the parameters. The UC subgroups of GDM fared better than PGDM as far as all complications and congenital anomalies were concerned. Compared with international data, there is a dichotomy of the results of GDM and PGDM.

CONCLUSIONS

For GDM patients all parameters may not be uniformly affected by the same degree of glycaemic control. A tight control may not be theonly factor to decide on the outcomes for PGDM patients.

Age-related macular degeneration is the leading cause of blindness in the Western world, and the pathophysiology of the condition is largely unknown. However, it shares many clinical and pathological features with Sorsby's fundus dystrophy (SFD), an autosomal dominant disease, known to be associated with mutations in the TIMP-3 gene. In Bruch's membrane of both conditions, there are molecular assemblies with distinct transverse bands occurring with a periodicity of about 100 nm. Similar assemblies were also found in the vitreous of a patient with full-thickness macular holes and were identified as being made of collagen VI. The assemblies found in the eye with SFD can be classified into two types, both with a 105-nm axial repeat, but one showing pairs of narrow bands about 30 nm apart and the other showing a single broad band in every repeat. By comparison with the assemblies in the vitreous, collagen VI is considered to be the most likely protein in these assemblies. Furthermore, both of the assemblies associated with SFD can be explained in terms of collagen VI tetramers, one in which the tetramers bind to the mutant tissue inhibitor of metalloproteinases-3 (the gene product of TIMP-3) and the other in which little or no binding occurs. TIMP-3 bound to collagen VI may be more resistant to degradation and create an imbalance between the normal amount of TIMP-3 and matrix metalloproteinases (the substrate of TIMPs) in Bruch's membrane with consequent disruption of the normal metabolic processes. Understanding the structure of these collagen VI/TIMP assemblies in Bruch's membrane may prove to be important for understanding the pathophysiology of age-related macular degeneration.

Prophylaxis against influenza could be improved by the development of a stable, easy to deliver, potent mucosal vaccine. In this study, we spray-freeze-dried (SFD) whole inactivated virus influenza vaccine (WIV) alone or supplemented with monophosphoryl lipid A (MPLA) using inulin as a lyoprotectant. Physical characterization revealed that the SFD powder consisted of highly porous particles with a size distribution suitable for pulmonary administration. The receptor-binding properties of WIV and the immunostimulatory properties of MPLA were preserved after spray-freeze-drying as indicated by unchanged hemagglutination titers and a retained ability of the vaccine to activate NFkB after incubation with a reporter cell line, respectively. Pulmonary vaccination of mice with MPLA-adjuvanted liquid or powder WIV resulted in induction of higher mucosal and systemic antibody concentrations than vaccination with non-adjuvanted formulations. When exposed to influenza virus, mice immunized with MPLA-adjuvanted pulmonary vaccine showed similar protection in terms of reduction in lung virus titers and prevention of weight loss as mice immunized intramuscularly with subunit vaccine. Characterization of the antibody response revealed a balanced IgG2a-to-IgG1 profile along with induction of both memory IgA- and IgG-producing B cells in mice immunized with MPLA-adjuvanted vaccine. These studies suggest that the mucosal and systemic immune responses to pulmonary delivered influenza vaccines can be significantly enhanced by using MPLA as adjuvant. MPLA-adjuvanted SFD vaccine was particularly effective implying that delivery of adjuvanted vaccine powder to the lungs can be an attractive way of immunization against influenza.

Although regular physical activity is an integral part of T2D management, few diabetic patients have a sufficient level of physical activity. However over the past decade or so, the beneficial effects of regular physical activity have been well demonstrated, both in T2D prevention (50% reduction in the incidence of T2D in subjects with high metabolic risk) as well as T2D management for the improvement of glycaemic control (mean 0.7% improvement of HbA1c) and the reduction of T2D-related comorbidities (improvement in blood pressure values and lipid profile, decrease in insulin resistance). Physical activity has both acute effects (effects of one exercise session) and more prolonged effects of exercise when it is repeated on a regular basis (training effect). In addition, the physical activity recommendations have been extended to a wide range of physical activities (by combining both endurance and muscle strengthening exercises), thus varying the physical activity practiced according to the patient's available time, practice sites, preferences and interests. Following a pathophysiology review, the effects of physical activity will be discussed and presented in terms of evidence-based medicine. The recommendations will be defined and practical prescribing information will be suggested, while taking into account that clinicians are concerned with answering questions regarding how, where and with whom: how can patients be motivated to practice a physical activity over the long-term? And how can qualified exercise trainers and appropriate practice settings be found?

BACKGROUND

The co-occurrence of generalized anxiety disorder and personality disorders suggests the existence of association between the neurobiological predispositions leading to the development of these disorders and activation of cytokine system. Pro-inflammatory chemokines such as CCL-5/RANTES (regulated upon activation normal T cell expressed and secreted) and CXCL12/SDF-1 (stromal derived factor) play an important role in immune response.

METHODS

A total of 160 participants were enrolled in the study, 120 of whom comprised the study group (people with the dual diagnosis of personality disorder and generalized anxiety disorder). The mean age was 41.4 ± 3.5 years (range: 20-44 years). The control group consisted of 40 healthy individuals in the mean age of 40.8 ± 3.1 years (range: 20-43 years). A blood sample was collected from each participant and the plasma levels of the CCL-2/MCP-1 (monocyte chemoattractant protein-1), RANTES and SDF-1 chemokines were determined by ELISA.

RESULTS

Increased levels of MCP-1 and SDF-1 were found both in women and in men versus the control group for all types of personality disorders. The levels of CCL-5 in men were significantly increased versus the control group and significantly higher in women than in men. Neither women nor men with avoidant or obsessive-compulsive personality disorder showed any significant differences in MCP-1 or SFD-1 levels. In subjects with borderline personality disorder, the levels of the study chemokines were higher in women than in men.

CONCLUSIONS

Our study has shown the need for determination of proinflammatory interleukins which are considered as biomarkers of personality disorders and generalized anxiety disorders.