Chitosan/HPMC-based mucoadhesive film co-loaded with fluconazole and ofloxacin for management of polymicrobial keratitis.

Bacterial and fungal co-infection leads to polymicrobial keratitis (PMK). The current study produced swellable mucoadhesive biopolymeric films composed of chitosan, HPMC, and glycerol using cast drying method. The film was dual-loaded with fluconazole (FCZ) and ofloxacin (OFX) to treat PMK. The prepared film exhibited excellent thickness, folding endurance, surface pH, tensile strength, and stability characteristics. In addition, it also exhibited good in vitro antimicrobial activity, ex-vivo mucoadhesion, and corneal permeation. AUC (0-∞) and MRT were 6.5 and 5.2-fold higher for a film containing FCZ and 22.5 and 2.5-fold higher for a film containing OFX than their marketed formulations. PK-PD simulation study supports desired efficacy of the proposed dosage form. Thus, the film exhibits longer pre-corneal drug residence time and enhanced ocular bioavailability, most likely resulting in high patient compliance. The proposed film could be a prominent replacement for the existing dosage form and may present a viable alternative for the treatment of PMK.

N-Alkyl/aryl-4-(3-substituted-3-phenylpropyl)piperazine-1-carbothioamide as dual-action vaginal microbicides with reverse transcriptase inhibition.

The growing population and health-care burden (due to STIs and HIV) imposes a particular economic crisis over resource-poor countries. Thus a novel approach as vaginal microbicides emerges as integrated tool to control both population and anti-STIs/HIV. Our continued efforts in this field led to the synthesis of fifteen N-alkyl/aryl-4-(3-substituted-3-phenylpropyl) piperazine-1-carbothioamide (12-26) derivatives as topical vaginal microbicides which were evaluated for anti-Trichomonas, spermicidal, antifungal and reverse transcriptase (RT) inhibitory activities. All compounds were also tested for preliminary safety through cytotoxicity assays against human cervical cell line (HeLa) and the vaginal flora, Lactobacillus. Docking studies were performed to gain an insight into the binding mode and interactions of the most promising compound 12 [oxo derivative], comprising of reverse transcriptase (RT) inhibitory (72.30%), spermicidal (MEC 0.01%), anti-Trichomonas (MIC 46.72 µM) and antifungal (MIC 9.34-74.8 µM) activities, along with its hydroxyl (17) and O-alkylated 4-trifluoromethylphenoxy (22) derivative, with similar activities. The stability of compound 12 in simulated vaginal fluid (SVF) and its preliminary in vivo pharmacokinetics performed in female NZ-rabbits signifies its clinical safety in comparison to marketed spermicide Nonoxynol-9.

Novel Glycoconjugate of 8-Fluoro Norfloxacin Derivatives as Gentamicin-resistant Staphylococcus aureus Inhibitors: Synthesis and Molecular Modelling Studies.

Antibiotic resistance has been the subject of interest in clinical practice due to high prevalence of antibiotic-resistant pathogenic organisms. In view of the prevalence of lesser resistance in antibiotics belonging to aminoglycoside class of compounds viz. Food and Drug Administration-approved gentamicin for the treatment of Staphylococcus infections, which also has instances of resistance in the clinical isolates of Staphylococcus aureus, a series of novel glycoconjugates of 8-fluoro norfloxacin analogues with high regio-selectivity by employing copper (I)-catalyzed 1, 3-dipolar cycloaddition of 1-O-propargyl monosaccharides has been synthesized and evaluated for the antibacterial activity against gentamicin resistance Staphylococcus aureus. Among these compounds, the compound 10g showed better antibacterial activity (MIC = 3.12 µg/ml) than gentamicin (Escherichia coli (12.5 µg/ml), Staphylococcus aureus (6.25 µg/ml) and Klebsiella pneumonia (6.25 µg/ml), including gentamicin resistant (>50 µg/ml) strain in vitro). The docking studies suggest DNA gyrase of Staphylococcus aureus as a probable target for the antibacterial action of compound 10g.

Design and synthesis of substituted morpholin/piperidin-1-yl-carbamodithioates as promising vaginal microbicides with spermicidal potential.

A series of seventeen morpholin/piperidin-1-yl-carbamodithioate (3-19) were synthesized as topical vaginal microbicidal spermicides. The synthesized compounds were evaluated for their anti-Trichomonas activity against MTZ susceptible and resistant strains along with their spermicidal and antifungal potential. All the synthesized compounds were assessed for their safety through cytotoxic assay against human cervical cell line (HeLa) and compatibility with vaginal flora, Lactobacillus. The study identified eleven dually active compounds with apparent safety. The plausible mode of action of these compounds was through sulfhydryl binding, confirmed via reduction in available free thiols on human sperm. The most promising compound 9 significantly inhibited (P<0.001) thiol-sensitive sperm hexokinase. The stability of compound 9 in simulated vaginal fluid (SVF) was performed via HPLC-PDA method, which supported its utility for vaginal administration.

Concurrent variations of median and musculocutaneous nerves and their clinical correlation--a cadaveric study.

Variations of median nerve, musculocutaneous nerve and their communicating branches are of interest for anatomists and surgeons. These variations may be vulnerable to damage in surgical procedures. We examined median nerve and musculocutaneous nerve concurrently in 58 cadavers, i.e. 116 superior extremities, and found median nerve innervating muscle of the anterior compartment of arm in the absence of musculocutaneous nerve in 11.2% superior extremities, splitting of median nerve in the arm into median nerve proper and musculocutaneous nerve in 5.12% superior extremities, and communication between median and musculocutaneous nerves in 20.7% superior extremities. Knowledge of such anatomical variations is helpful for surgeons treating neoplasm or repairing trauma.

Prevalence of obesity, physical inactivity and undernutrition, a triple burden of diseases during transition in a developing economy. The Five City Study Group.

OBJECTIVE AND DESIGN: The objective of the study was to find out the prevalence of overweight, obesity, undernutrition and physical activity status in the urban populations of India. Cross-sectional surveys were conducted in 6-12 urban streets in each of five cities in five different regions of India using a common study protocol and criteria of diagnosis. SUBJECTS AND METHODS: A total of 6940 subjects (3433 women and 3507 men) aged 25 years and above were randomly selected from the cities of Moradabad (n = 2002),Trivandrum (n = 1602), Calcutta (n = 900), Nagpur (n = 894) and Bombay (n = 1542). Evaluation and validation were performed by a physician and dietitian-administered questionnaire at Moradabad. After pooling of data, all subjects were divided into various age groups for men and women. Obesity (body mass index = 30 > kg/m(2)) and overweight (BMI 2 25-29.9 kg/m(2) and > 23 kg/m(2)) as well as waist-hip ratio (> 0.85 in women and > 0.88 in men, central obesity) were calculated and physical activity status assessed by a validated questionnaire. RESULTS: The overall prevalence of obesity was 6.8% (7.8 vs. 6.2%, P < 0.05) and overweight 33.5% (35.0 vs. 32.0%, P < 0.05) among women and men, respectively. The highest prevalence of obesity (7.8%) and overweight (36.9%) was found among subjects aged 35 to 44 years in both sexes. The prevalence of obesity was significantly (P < 0.05) greater in Trivandrum (8.5%), Calcutta (7. 1%) and Bombay (8.3%) compared to Moradabad (6.2%) among women and in Trivandrum (7.4%) and Bombay (7.2%), compared to Nagpur (5.0%) among men. There was a significant decreasing trend in obesity (P < 0.05) and overweight (P < 0.05) with increasing age above 35-44 years in both sexes. The overall prevalence of subjects > 23 kg/m(2) was 50.8% and central obesity 52.6%. The overall prevalence of sedentary behaviour was 59.3% among women and 58.5% among men. Both sedentary behaviour and mild activity showed a significant increasing trend in women after the age of 35-44 years. In men, such a trend was observed above the age of 45 years. Sedentary behaviour was significantly (P < 0.05) greater in Trivandrum, Calcutta, and Bombay compared to Nagpur. Sedentary behaviour was significantly (P < 0.001) associated with obesity in both sexes, compared to non-obese men and women. The overall prevalence of undernutrition was 5.5% (n = 380) which was significantly more common in Moradabad, north and Nagpur, central India compared to other cities. CONCLUSIONS: Obesity, overweight and central obesity and sedentary behaviour coexist with undernutrition, and have become a public health problem in all the five cities of India. The prevalence of obesity and sedentary behaviour was significantly greater in Trivandrum, Calcutta and Bombay compared to Moradabad and Nagpur. Sedentary behaviour was significantly associated with obesity compared to non-obese subjects in both sexes, which may be due to greater economic development in metro cities.

Social class and all-cause mortality in an urban population of North India.

BACKGROUND: There is a rapid emergence of cardiovascular disease in India with economic development, leading to an increase in mortality due to these diseases. The exact causes of death in India, however, are not known. SUBJECTS AND METHODS: We studied randomly selected death records from 2222 (1385 men and 837 women) victims, aged 25-64 years, out of 3034 death records during 1999-2001 at the Municipal Corporation, Moradabad. All the families of these victims could be contacted individually to find out the causes of death, by scientists/doctors-administered pre-tested verbal autopsy questionnaires, completed with the help of spouses and local treating doctors practising in the concerned lane. Social classes were assessed by a questionnaire based on attributes of per capita income, occupation, education, housing and ownership of consumer luxury items in the household. RESULTS: Causes of mortality included infectious diseases (41.1%, n = 915) such as tuberculosis, pneumonia, chronic obstructive pulmonary disease, diarrhea/dysentery, hepatitis B, and inflammatory brain infections as the commonest causes of death in the urban population of North India. The second most common causes of death were circulatory diseases (29.1%, n = 646), including heart attacks (10.0%), strokes (7.8%), valvular heart disease (7.2%, n = 160), sudden cardiac death, and inflammatory cardiac disease (each 2.0%, n = 44). Malignant neoplasm (5.8%, n = 131), injury (14.0%, n = 313), including accidents, fire and falls, and poisonings were also quite common causes of death. Miscellaneous causes of death were noted in 9.1% (n = 202) death records, including diabetes mellitus (2.2%, n = 49), suicides (1.8%, n = 41), congenital anomalies (1.0, n = 37), dental caries infections (1.9, n = 42), and burns (1.3%, n = 33). Pregnancy and perinatal causes (0.72%, n = 15) were not commonly recorded in our study. Circulatory diseases as the cause of mortality were statistically significantly more common among higher social classes (1-3) than in lower social classes (4 and 5) whose members died more often due to infections. Heart attacks, strokes, hypertension, diabetes and obesity were statistically significantly more common among higher social classes (1-3) as compared to classes 3 and 4, but tobacco intake showed only minor differences among various classes. CONCLUSIONS: This study indicates that circulatory diseases, injury and malignant diseases have become the major causes of death in India, after infections. Members of social classes 1-3 died more often due to circulatory diseases and members in lower social classes died more often due to infections. Urbanization with rapid changes in diet and lifestyle in various social classes, and possibly aging of the population seem to be responsible for the double burden of diseases, related to under- and over-nutrition, causing death in a developing economy. Monitoring of blood pressure and heart rate around the clock for 7 days, with data analysed chronobiologically can detect abnormal circadian patterns associated with a large increase in cardiovascular disease risk, greater than hypertension itself, allowing the institution of prophylactic treatment. Such prehabilitation may be particularly useful to curb the increasing burden of cardiovascular diseases in both developed and developing countries.