Neuroprotective effect of metformin in MPTP-induced Parkinson's disease in mice.

Metformin a well known antidiabetic drug has been recently investigated and proposed to promote neurogenesis and enhance the spatial memory formation. In the present study, we aim to investigate the neuroprotective effect of metformin with respect to Parkinson's disease (PD). MPTP (Sigma-Aldrich, St. Louis, MO, USA) (25mg/kg) along with Probenecid (250 mg/kg) was administrated for five consecutive days to induce Parkinsonism in mice. Metformin 500 mg/kg was administrated orally for 21 days. Motor co-ordination and locomotor activities were evaluated by rotarod and open-field tests. The oxidative stress levels were assessed by estimating the activity of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and lipid peroxidation (LPO) specifically in the midbrain. Dopaminergic degeneration was evaluated by analyzing the tyrosine hydroxylase (TH) by immunostaining and nissl staining of the substantia nigra (SN) region of the brain. In addition brain-derived neurotrophic factor (BDNF) was also estimated. Our findings demonstrated that long-term metformin treatment resulted in significant improvement of the locomotor and muscular activities in MPTP-treated mice than acute treatment. Metformin treatment significantly improved the antioxidant activity as compared to MPTP-treated group. TH-positive cells decreased up to 16% in MPTP-treated mice as compared to normal mice (P<0.001) and were found to be protected from degeneration in metformin-treated mice (47%, P<0.01). Interestingly, BDNF levels were found to be significantly elevated in metformin treatment group as compared to MPTP treatment mice (P<0.001). In conclusion, metformin possesses neuroprotective activity and provides preclinical support for therapeutic prospective of this compound in the treatment of PD.

Comparative evaluation of effect of polymerizable and non-polymerizable desensitizing agents on crown-retentive-strength of zinc-phosphate, glass-ionomer and compomer cements.

The Purpose of this study was to evaluate the effect of polymerizable and non-polymerizable dentine desensitizers on retention of complete cast crowns cemented with three different types of cements. Freshly extracted human molars (n = 90) were prepared for standardized crown preparation (6-degree taper 4-mm height). The axial surface area of each preparation was determined and specimens were distributed equally among groups (n = 10). Dentine desensitizers, cementing agents, glass ionomer cement and compomer cement. Teeth were prepared and individual castings were made using high noble porcelain-metal alloy. Castings were cemented, thermo-cycled and removed along the path of insertion using a universal testing machine. Tooth surface as well as inner surface of the casting was examined and nature of cement failure was determined. Compomer cement exhibited the highest retentive strength and all dentine treatments resulted in significantly different retentive values. Zinc phosphate was the least retentive. Crown retentive values of Compomer cement were improved with Prime & Bond NT and Gluma Desensitizer Retentive values of zinc phosphate cement with Prime & Bond NT were decreased and not affected with Gluma Desensitizer Retentive values of Glass ionomer cement were not affected by any of the desensitizers used in the study.

Age assessment from mandible: comparison of radiographic and histologic methods.

Age assessment is an integral and important aspect of forensic odontology. The use of long bones and teeth has been documented since decades. The aim of this study was to use both radiographic and histologic methods of age estimation and to determine which method gives a near actual age. Orthopantomograph (OPG) was used to study the radiographic changes and ground sections were made for histologic study. Of the various parameters studied, we concluded that the histologic parameters recorded ages, which were closer to the actual age. Of the histologic parameters, two to three parameters when combined were still better.

Pitot-tube flowmeter for quantification of airflow during sleep.

The gold-standard pneumotachograph is not routinely used to quantify airflow during overnight polysomnography due to the size, weight, bulkiness and discomfort of the equipment that must be worn. To overcome these deficiencies that have precluded the use of a pneumotachograph in routine sleep studies, our group developed a lightweight, low dead space 'pitot flowmeter' (based on pitot-tube principle) for use during sleep. We aimed to examine the characteristics and validate the flowmeter for quantifying airflow and detecting hypopneas during polysomnography by performing a head-to-head comparison with a pneumotachograph. Four experimental paradigms were utilized to determine the technical performance characteristics and the clinical usefulness of the pitot flowmeter in a head-to-head comparison with a pneumotachograph. In each study (1-4), the pitot flowmeter was connected in series with a pneumotachograph under either static flow (flow generator inline or on a face model) or dynamic flow (subject breathing via a polyester face model or on a nasal mask) conditions. The technical characteristics of the pitot flowmeter showed that, (1) the airflow resistance ranged from 0.065 ± 0.002 to 0.279 ± 0.004 cm H(2)O L(-1) s(-1) over the airflow rates of 10 to 50 L min(-1). (2) On the polyester face model there was a linear relationship between airflow as measured by the pitot flowmeter output voltage and the calibrated pneumotachograph signal a (ß(1) = 1.08 V L(-1) s(-1); ß(0) = 2.45 V). The clinically relevant performance characteristics (hypopnea detection) showed that (3) when the pitot flowmeter was connected via a mask to the human face model, both the sensitivity and specificity for detecting a 50% decrease in peak-to-peak airflow amplitude was 99.2%. When tested in sleeping human subjects, (4) the pitot flowmeter signal displayed 94.5% sensitivity and 91.5% specificity for the detection of 50% peak-to-peak reductions in pneumotachograph-measured airflow. Our data validate the pitot flowmeter for quantification of airflow and detecting breathing reduction during polysomnographic sleep studies. We speculate that quantifying airflow during sleep can differentiate phenotypic traits related to sleep disordered breathing.

Developing quantitative physiological phenotypes of sleep apnea for epidemiological studies.

Existing physiological databases have not been sufficiently detailed to provide relevant and important information for characterizing the pathophysiology of obstructive sleep apnea. Critical collapsing pressure (P(CRIT)) is a standard method for determining upper airway patency during sleep, however is labor intensive and prohibits large-scale studies. Based on previously published data indicating R(US) does not significantly vary between groups, our aim was to develop an approach to estimate the P(CRIT) from airflow at atmospheric pressure (V(atm)). In a dataset of 126 subjects, where P(CRIT) and R(US) were measured using standard techniques. We then determined the minimum sample size required to estimate the R(US) mean and variance by utilizing a bootstrap procedure (30 times for n=3 to 126). We first estimated the minimum number of subjects needed for obtaining a group for a two-tailed (z=1.96) standard error for R(US) in the population. Then in 75 individuals, quantitative estimates of airflow were obtained at atmospheric pressure. Using the estimated R(US) and atmospheric, we determined an estimated P(CRIT) (ЄP(CRIT)). Bland-Altman plots were generated to determine the agreement between the measured P(CRIT) and ЄP(CRIT). For the entire population the mean ± SEM R(US) was 23 ± 1 cmH(2)O/L/s (± 95% CI: 21, 25). ~40 subjects represent the minimum sample required to estimate the population variance within ± 2 SEM. In the subsample with atmospheric flow measurements, a linear regression model (ЄP(CRIT) [cmH(2)O] = V(@PN) [L/s]x-23[cmH(2)O/L/s]), ЄP(CRIT) ranged from 0 to -9.6 cmH(2)O. In the Bland-Altman analysis there was no mean difference between the measured P(CRIT) and ЄP(CRIT) (-0.01 cmH(2)O; p=0.8) with upper and lower limits of agreement at ± 2.3 cmH(2)O. The variance of upstream resistance approaches a constant value in groups with approximately 40 subjects. Utilizing a fixed up-stream resistance to estimate P(CRIT) from the airflow at atmospheric pressure agrees with the measured values. These data suggest that measurements of quantitative airflow during standard polysomnography can be used to determine upper airway properties in large cohorts.

Inspiratory duty cycle responses to flow limitation predict nocturnal hypoventilation.

Upper airway obstruction (UAO) can elicit neuromuscular responses that mitigate and/or compensate for the obstruction. It was hypothesised that flow-limited breathing elicits specific timing responses that can preserve ventilation due to increases in inspiratory duty cycle rather than respiratory rate. By altering nasal pressure during non-rapid eye movement (non-REM) sleep, similar degrees of UAO were induced in healthy males and females (n = 10 each). Inspiratory duty cycle, respiratory rate and minute ventilation were determined for each degree of UAO during non-REM sleep and compared with the baseline nonflow-limited condition. A dose-dependent increase in the inspiratory duty cycle and respiratory rate was observed in response to increasing severity of UAO. Increases in the inspiratory duty cycle, but not respiratory rate, helped to acutely maintain ventilation. Heterogeneity in these responses was associated with variable degrees of ventilatory compensation, allowing for the segregation of individuals at risk for hypoventilation during periods of inspiratory airflow limitation. Upper airway obstruction constitutes a unique load on the respiratory system. The inspiratory duty cycle, but not the respiratory rate, determine the individual's ability to compensate for inspiratory airflow limitation during sleep, and may represent a quantitative phenotype for obstructive sleep apnoea susceptibility.

Metabolic syndrome in railway employees and its relation to lifestyle factors.

BACKGROUND: Limited information is available about the prevalence of the metabolic syndrome(MeTS) in India. Railway employees provided a unique opportunity to study the prevalence of MeTS in a variety of jobs. METHODS: A total of 995 railway employees, 872 males (mean age 42.96 +/- 7.91) and 123 females (mean age 44.28 +/- 7.91), underwent physical examination and anthropometric measurement for waist circumference; 605 males and 95 females also underwent biochemical examination. MeTS was diagnosed using ATP III criteria modified for Indians. RESULTS: The prevalence of MeTs in males was 162/605 (26.77%) and in females 26/95 (27.36%). Amongst all components of MeTS, high waist circumference was most prevalent in females (89.83%) and systolic hypertension in males (61.12%). In multivariate analysis, waist circumference in both genders had good association with sedentary job (P < 0.02), high fasting blood sugar (P < 0.02), age 45 years or older (P < 0.001), high systolic blood pressure (P < 0.001), high diastolic blood pressure (P < 0.001), physical inactivity (P < 0.001), while the correlation of dyslipidemia (low HDL and high triglycerides) with high waist circumference was not statistically significant. CONCLUSION: These results from a representative sample of Solapur division railway employees show that the MeTs is highly prevalent mainly in sedentary workers aged 45 years or older. The large numbers of Indian Railway employees with the MeTs may carry important implications for the health care sector.

Microcystic adenoma of pancreas: a case report.

Microcystic adenomas of the pancreas are rare benign neoplasms that occur most frequently in elderly females. Characteristically, the tumors have a spongy gross appearance and are composed of innumerable cysts lined by flat, and cuboidal cells which are rich in glycogen. They commonly present with abdominal discomfort or pain. In this case report, we present a cystic neoplasm of pancreas in a 65-year-old lady who clinically presented with discomfort in the abdomen and hyperglycaemia. Proximal pancreatectomy was done. Histopathological examination of surgical specimen confirmed the diagnosis of "Microcystic Adenoma ofPancreas". Despite of the rarity, microcystic adenoma should kept in the mind as the differential diagnosis of cystic lesions of pancreas.

Cervical thymic cyst: a case report.

Cervical thymic cysts are rare benign lesions. It should be considered in the differential diagnosis of cervical cysts in paediatric age group. This paper presents a case of a 6 years male child who presented with gradually increasing painless mass on right side of neck. Surgical excision was done. Histopathological study revealed features diagnostic of thymic cyst. It was clinically diagnosed as branchial cleft cyst. Though rare, thymic cysts should be included in the differential diagnosis of neck masses, especially in children.

The use of intravitreal bevacizumab in neovascular glaucoma: a case report.

PURPOSE: To assess the short-term safety and efficacy of an intravitreal injection of bevacizumab in a patient with neovascular glaucoma. CASE REPORT: Intravitreal bevacizumab injection was given in a patient with neovascular glaucoma and the changes in the visual acuity, intraocular pressure (lOP), iris neovascularisation were noted before injection and after one day, one week, three weeks and six weeks. Regression of the iris new vessels and normalization of the intraocular pressure was noted. CONCLUSION: Intravitreal bevacizumab was effective and safe in the short-term in a patient with neovascular glaucoma. It may be a useful adjunctive treatment.

Women have a greater ventilatory responses to upper airway obstruction than men.

We examined whether gender specific differences exist in defending inspiratory tidal volumes in the face of upper airway obstruction. In normal weight- and aged-matched men (n=9) and women (n=9), we induced upper airway obstruction with inspiratory flow limitation during NREM sleep by exposing individuals to sub-atmospheric nasal pressure. The mean inspiratory airflow was used to define three distinct levels of upper airway obstruction, based on a mean inspiratory airflow of 175-225 ml/s, 125-175 ml/s and 75-125 ml/s. While duty cycle responses were similar between genders, women had a greater response in T(TOT) at all flow limited conditions. (p<0.05). However, the greater response in T(TOT) led to a more pronounced decline in tidal volume in women compared to men (p<0.05), particularly during the mild and moderate upper airway obstruction. Our data demonstrate that the respiratory rate determines the tidal volume during periods of upper airway obstruction and indicate that individuals with a higher respiratory rate are at risk to develop hypoventilation in face of upper airway obstruction. Because women have a more brisk response in the respiratory rate than men, this may explain the difference in the expression of sleep disordered breathing between genders.

Selective acylation of 2 methoxynaphthalene by large pore zeolites: catalyst selection through molecular modeling.

The selective acylation of 2-methoxynaphthalene (2-MON) is commercially very important to produce selectively 2-acyl-6-methoxynaphthalene (2,6-AMON), which is a precursor to Naproxen, an anti-inflammatory drug. Most of the laboratory investigations conducted with different solid acids show that the undesirable products are formed in large quantities. Thus, various molecular modeling techniques were used to investigate selectivity towards desired 2,6-AMON isomer over undesired 1,2-AMON, in four large-pore zeolites, namely, mordenite (MOR), zeolite L (LTL), zeolite beta (BEA) and ITQ-7 (ISV). The qualitative results were obtained by using simple molecular graphics (MG) and structural fitting approach. The quantitative results were obtained by incorporating the interaction of atoms of the molecules and those of the zeolite frameworks. From diffusion energy profile calculations the diffusion energy barriers for self-diffusion of 2-MON and the acylated isomers were obtained. From these energy barrier values the selectivity offered by zeolites towards desired product was determined and it was found to be in the order of ISV>BEA>MOR>LTL. Hybrid Quantum Mechanics-Molecular Mechanics (QM/MM) approach was used to study the effect of Brønsted acidity on the activity and selectivity offered by zeolites. The interaction of the reactant and product species with the acidic protons at T3 and T9 sites in BEA, having different acidities was studied by this method. The QM energy values indicate that acidity affected the catalytic activity but not the regioselectivity towards the desired 2,6-AMON isomer.

Hypercapnic duty cycle is an intermediate physiological phenotype linked to mouse chromosome 5.

We hypothesized that upper airway obstruction (UAO) leads to a compensatory increase in the duty cycle [ratio of inspiratory time to respiratory cycle length (Ti/Tt)], which is determined by genetic factors. We examined the compensatory Ti/Tt responses to 1). UAO and hypercapnia among normal individuals and 2). hypercapnia in different inbred strains, C3H/HeJ (C3) and C57BL/6J (B6), and their first- and second-generation (F2) offspring. 3). We then used the compensatory Ti/Tt response in the F2 to determine genetic linkage to the mouse genome. First, normal individuals exhibited a similar increase in the Ti/Tt during periods of hypercapnia (0.11 +/- 0.07) and UAO (0.09 +/- 0.06) compared with unobstructed breathing (P < 0.01). Second, the F2 offspring of C3 and B6 progenitors showed an average Ti/Tt response to 3% CO2 (0.42 +/- 0.005%) that was significantly (P < 0.01) greater than that of the two progenitors. Third, with a peak log of the odds ratio score of 4.4, Ti/Tt responses of F2 offspring are genetically linked to an interval between 58 and 64 centimorgans (cM) on mouse chromosome 5. One gene in the interval, Dagk4 at 57 cM, is polymorphic for C3 and B6 mice. Two other genes, Adrbk2 at 60 cM and Nos1 at 65 cM, have biological plausibility in mechanisms of upper airway patency and chemosensitivity, respectively. In summary, Ti/Tt may serve as an intermediate physiological phenotype for compensatory neuromuscular response mechanisms for maintaining ventilation in the face of UAO and hypoventilation and to help target specific candidate genes that may play a role in the expression of sleep-disordered breathing.

Determination of celecoxib in pharmaceutical formulations using UV spectrophotometry and liquid chromatography.

A new UV spectrophotometric method (UV method) and a reversed phase liquid chromatographic method (LC method) for the quantitative estimation of celecoxib, a selective COX-2 inhibitor, in pure form and in solid dosage form were developed in the present study. The linear regression equations obtained by least square regression method, were Abs=4.949 x 10(-2).Conc. (in microg/ml)+1.110 x 10(-2) for the UV method and Area under the curve=5.340 x 10(1).Conc. (in ng/ml)+3.144 x 10(2) for the LC method, respectively. The detection limit, as per the error propagation theory, was found to be 0.26 microg/ml and 25 ng/ml, respectively, for the UV and LC methods. The developed methods were employed with a high degree of precision and accuracy for the estimation of total drug content in three commercial capsule formulations of celecoxib. The results of analysis were treated statistically, as per International Conference on Harmonisation (ICH) guidelines for validation of analytical procedures, and by recovery studies. The results were found to be accurate, reproducible and free from interference and better than the earlier reported methods.

Chickpea: a major food allergen in the Indian subcontinent and its clinical and immunochemical correlation.

BACKGROUND: The food allergy pattern of a country is influenced by the foods most commonly consumed. In India, the majority of the population consumes a vegetarian diet made up of pulse (legumes), cereals, and vegetables. In contrast to many western countries, chickpea preparations are consumed in large quantities in India. This study reports for the first time chickpea hypersensitivity reactions diagnosed with in vivo and in vitro tests. METHODS: One thousand four hundred patients visiting allergy clinics were randomly selected for the study. Those patients reporting an allergic reaction on every occasion after eating chickpea were considered history-positive. Modified prick tests were performed with chickpea and other members of the legume family on all these patients. The claims of the history-positive patients were verified with double-blind, placebo-controlled food challenges (DBPCFCs). Proteins in chickpea extracts were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred on nitrocellulose paper. Serum specimens from history-positive patients were analyzed by immunoblot and ELISA. To verify the IgE specificity, an immunoblot inhibition assay was also performed. RESULTS: Of the 1,400 patients screened, 142 patients were history-positive to some food and 59 of these implicated chickpeas. Forty-one patients were skin test-positive and 31 were DBPCFC-positive for chickpea. The predominant symptoms after chickpea ingestion were respiratory. The ELISA results did not correlate well with the DBPCFC results; however, the skin test results correlated with DBPCFC in 75% of patients. Immunoblot analysis showed that 70, 64, 35, and 26 kD proteins were major allergens. CONCLUSIONS: Chickpea is an important source of allergen that can cause IgE-mediated hypersensitivity reactions ranging from rhinitis to anaphylaxis.

Osteoclastoma like giant cell tumour of the thyroid--a variant of undifferentiated carcinoma--a case report.

A case of osteoclastoma like giant cell tumour of thyroid is reported in a patient who presented with dysphagia and swelling in the neck. The light microscopy showed numerous osteoclast-like giant cells embedded in mononuclear stromal cells, the overall appearance resembling that of giant cell tumour of bone.

Allergy to fenugreek (Trigonella foenum graecum).

BACKGROUND: Allergic reactions after consumption of spices are well-known. In Asia, fenugreek seeds are consumed as spices and also as medicines. Literature survey carried out does not reveal reports of allergic reactions to fenugreek. In our survey carried out on patients with food allergy, we found two cases of severe allergy to fenugreek. METHODS: We report here two cases of immediate allergy following ingestion, inhalation, and external application of fenugreek seed powder. In the first case, inhalation of the fenugreek seed powder resulted in rhinorrhea, wheezing, and fainting. The second case was of a patient with chronic asthma who developed numbness of head, facial angioedema, and wheezing after application of fenugreek paste to her scalp as a treatment for dandruff. Skin scratch test was performed with fenugreek and other members of the Leguminosae family as fenugreek also belongs to Leguminosae. Objective evidence of the reaction was obtained by conducting double-blind placebo-controlled challenges (DBPCFC). For detecting IgE binding by immunoblotting method, the proteins of the fenugreek extract were resolved using sodium dodecyl sulphate polyacrylamide gel electrophoresis. RESULTS: Skin scratch tests for the patients revealed strong sensitivity to fenugreek and chickpeas. None of the controls showed such response with fenugreek extract. During DBPCFC, both patients showed > 20% drop in peak flow rate after consumption of fenugreek and chickpea. Immunoblots demonstrated binding of specific IgE from the patients' sera with the protein from extracts between 20 kD to 70 kD bands. CONCLUSION: This case report has enlarged the list of food allergens with the addition of fenugreek.