In Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model.

Colonic drug delivery is intended not only for local treatment in inflammatory bowel disease (IBD) but also for systemic delivery of therapeutics. Intestinal myeloperoxidase (MPO) determination could be used to estimate the average level of inflammation in colon as well as to determine the efficacy of drugs to be used in the treatment of inflammatory bowel diseases or study the specificity of dosage forms to be used for colonic targeting of anti-inflammatory drugs. Colonic prodrug sulfasalazine (SASP) gets metabolized to give 5-aminosalicylic acid (5-ASA), which is the active portion of SASP. However, when given orally, 5-ASA is absorbed in upper part of gastrointestinal tract (GIT) and not made available in colon. In the present study, colon-targeted delivery of 5-ASA was achieved by formulating tablets with two natural polymers namely guar gum and pectin using compression coating method. Colonic specificity of 5-ASA tablets (prepared using guar gum and pectin as polymers) was evaluated in vitro using simulated fluids mimicking in vivo environment as well as in vivo method using chemically (2,4,6-trinitrobenzenesulfonic acid and acetic acid)-induced colitis rat model. Both colon-specific formulations of 5-ASA (guar gum and pectin) were observed to be more effective in reducing inflammation in chemically induced colitis rat models when compared to colon-specific prodrug sulfasalazine as well as conventional 5-ASA administered orally.

Safety Profile of a Polyherbal Formulation (Gynocare capsules) in Female Rats by Subchronic Oral Toxicity Study.

Gynocare capsules, is a polyherbal formulation, are used as uterine tonic and for treating gynaecological ailments like infertility, leucorrhea, and menstrual disorders. The formulation contains ingredients of herbal origin, such as, extracts of Ashoka, Vasaka, Durva, Chandan, Musk, and so on. It was evaluated for its safety at the therapeutic dose level by a repeated dose oral toxicity study in albino Wistar rats. The herbal formulation was administered orally at a therapeutic dose of 100 mg/kg/day, for 90 days. All animals were monitored daily for their health status and signs of abnormalities. The body weight, water consumption, and food intake were measured once weekly. At the end of the experimental period, various hematological and biochemical parameters were estimated and histopathologies of selected organs were conducted. The study resulted from the long-term oral administration of Gynocare capsules (100 mg/kg), did not cause any relevant signs of toxicity nor significant changes in the physical, hematological and biochemical parameters. However, statistically significant differences were seen in the relative organ weights of adrenal gland, ovary, and serum creatinine levels. The reduction in ovary weight revealed the possibility of the drug targeting the ovary. Moreover, no pathological features were identified in the treated group as monitored by the histopathological analysis of the internal organs. The study established that Gynocare capsules at the dose given (100 mg/kg) did not induce any remarkable or significant toxic effects, indicating that it was safe in rats following oral administration for 90 consecutive days.

Evaluation of the insect growth regulator Lufenuron (Match®) for control of Aedes aegypti by simulated field trials.

The insect growth regulator, Lufenuron, at concentrations of even multiples of LC(90) (determined under laboratory conditions) was tested against the III instar larvae of Aedes aegypti under simulated field conditions. For all concentrations tested, 100 % mortality of the larvae was observed within 24 h of exposure to Lufenuron-treated water. In experiments with LC(90) × 4 Lufenuron concentration and where 15 % of water volume was replaced daily, percent mortality of the larvae was reduced to 40 % after the 54th day of treatment. Percentage mortality of the III instar larvae on the 54th day was higher in water with LC(90) × 6 concentration than that observed for water with LC(90) × 4 of Lufenuron. In the experiments with LC(90) × 4 and LC(90) × 6 concentrations of Lufenuron where 15 % of water volume was replaced weekly, larval mortality obtained after the eighth week was 68.75 and 88.33 %, respectively. In LC(90) × 4 and LC(90) × 6 of Lufenuron-treated stagnant water (without replacement of water), the percent mortality of the larvae on the 55th day was 65 and 90 %, respectively. Introducing a fresh batch of III instar A. aegypti larvae in the Lufenuron-treated waters revealed that residual activity of Lufenuron was sustained for 45 days after the treatment. All these experiments revealed that Lufenuron not only affects the prevalence of the A. aegypti larvae but also induces the development of abnormal adults.

Design and evaluation of liposomal formulation of pilocarpine nitrate.

Prolonged release drug delivery system of pilocarpine nitrate was made by optimizing thin layer film hydration method. Egg phosphatidylcholine and cholesterol were used to make multilamellar vesicles. Effects of charges over the vesicles were studied by incorporating dicetylphosphate and stearylamine. Various factors, which may affect the size, shape, encapsulation efficiency and release rate, were studied. Liposomes in the size range 0.2 to 1 µm were obtained by optimizing the process. Encapsulation efficiency of neutral, positive and negatively charged liposomes were found to be 32.5, 35.4 and 34.2 percent, respectively. In vitro drug release rate was studied on specially designed model. Biological response in terms of reduction in intraocular pressure was observed on rabbit eyes. Pilocarpine nitrate liposomes were lyophilized and stability studies were conducted.

Albumin microspheres as an ocular delivery system for pilocarpine nitrate.

Pilocarpine nitrate loaded egg albumin microspheres were prepared by thermal denaturation process in the size range of 1-12 mum. A series of batches were prepared to study factors, which may affect the size and entrapment efficiency of drug in microspheres and optimized the process. Drug loaded microspheres so obtained were evaluated for their size, entrapment efficiency, release rate and biological response. Electron photomicrographs were taken (8000X) to study the morphological characteristics of microspheres. The entrapment and encapsulation of pilocarpine after process optimization was found to be 82.63% and 62.5% respectively. In vitro dissolution rate studies revealed that the release of drug from the microspheres followed spherical matrix mechanism. Biological response of microspheric suspension was measured by reduction in intraocular pressure in albino rabbit eyes and compared with marketed eye drops. Various pharmacokinetic parameters viz. onset of action, duration of action, Tmax and AUC were studied. A measurable difference was found in the mean miotic response, duration and AUC of pilocarpine nitrate microspheric suspension.

Cirumstances and motivations for seeking abortions: a community based study in Chandrapur District, Maharashtra.

The present population based group comparison study was undertaken to study the circumstances, motivations and influencing factors for seeking abortion in women in Chandrapur District of Maharashtra. Participants of the study included 500 cases of induced abortion and the equal number of normal delivered women during the same period and in the same area as comparison group. Having two children, domestic problems and unwanted pregnancy were conditions acceptable to study subjects to terminate the pregnancy. Family and domestic problems, poor socio-economic status, short inter-pregnancy interval and completed family size were some of the important reasons quoted by study subjects for not desiring to continue the current pregnancy. Majority of the subjects felt that the decision to terminate or keep pregnancy is usually taken jointly by both the husband and wife. Family and domestic problems, poor socioeconomic status and short inter pregnancy interval were the important reasons quoted by abortion cases for seeking abortion in the current pregnancy. Only 1.80% of the cases reported failure of contraceptive method as a cause of seeking abortion services. In 78.4% of abortion cases as compared to 5.4% subjects from the comparison group, pregnancy was un-planned.

Factors responsible for delayed immunisation among children under 5 years of age.

Although immunisation coverage has increased substantially in recent years, still a sizable proportion of children are not being immunised at appropriate time. The present hospital based, pair matched, case control study was carried out at immunoprophylactic centre of Government Medical College and Hospital, Nagpur, to identify risk factors associated with delayed immunisation among children. This study included 139 children with a delay of more than 90 days for scheduled primary immunisation and equal number of matched control (for dose) receiving immunisation at appropriate time. The study identified significant association of family size [Odd's ratio (OR) = 7.3, 95% confidence interval (CI) = 1.5-35.6], number of children < 5 years (OR = 3.17, 95% CI = 1.1-9.9), sex (OR = 3, 95% CI = 1.2-7.4), paternal education (OR = 3.7, 95% CI = 1.6-8.5), maternal education (OR = 4, 95% CI = 1.5-10.9), socio-economic status (OR = 3.7, 95% CI = 1.1-13.2) and distance from health centre (OR = 4.7, 95% CI = 1.2-17.6) with delayed immunisation. Negligence (56%) and unawareness (22.7%) of parents were main reasons for delayed immunisation. Hence more stress on identified risk factors in the study will indirectly help in reducing the frequency of delayed immunisation.

Renal cell carcinoma as significant manifestation of tuberous sclerosis complex.

We present a case of renal cell carcinoma diagnosed in 1982; aged 20 years. Regular follow up of the abdomen by USG noted first the presence of 2 nodules in the remaining kidney in 1994, age 30 and more lesions in 1997, aged 35. These were suspected to be angiomyolipomas on USG. The radiologist on this basis raised the question of tuberous sclerosis. Subsequent evaluation by internist/neurologist showed few adenoma sebaceum lesions a single ash leaf macule, a shagreen patch on the back, and characteristic multiple subependymal calcifications diagnostic of tuberous sclerosis on CT scan brain. The mentation was normal, there was history of only a single fit in childhood. The renal cell carcinoma was thus the first significant manifestation of tuberous sclerosis complex (TSC).

Microporous membrane drug delivery system for indomethacin.

Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of rheumatoid arthritis for more than a decade. The high incidence and severity of side effects, which are dose-related and associated with long-term administration, have limited its use. This has led to the search for new delivery systems which can overcome the side effects by controlling the drug release. In this study, Indomethacin Extended Release Formulation was developed by pelletization using the method of extrusion/spheronization. The drug containing pellets were further coated to achieve the required release profile as per USP. Coating systems developed on the principle of microporous membrane drug delivery using soluble salt gave the best results.

In vitro evaluation on inhibitory nature of some Neem formulations against plant pathogenic fungi.

Different Neem formulations derived from the Neem tree (Azadirachta indica) have been found to be potential fungicides against a broad spectrum of plant pathogenic fungi. Some Neem formulations viz. Achook (0.15% EC), Bioneem (0.03% EC), Nimbecidine (0.03% EC) and Neemark (0.03% EC) were examined against some plant pathogenic fungi such as (Fusarium oxysporum, Alternaria solani, Curvularia lunata, Helminthosporium sp. and Sclerotium rolfsii). Among these Achook (0.15% EC) was found to be more active in terms of Minimum Inhibition Concentration (MIC) value followed by Bioneem, Neemark and Nimbecidine. Remarkably, although all these formulations are oil based, Neem oil itself did not exhibit any fungicidal activity.

A prediction model for moderate or severe dehydration in children with diarrhoea.

A hospital-based unmatched case-control study (387 cases and 387 controls) was carried out at the Government Medical College Hospital, Nagpur, India, to devise and validate a risk-scoring system for predicting the development of moderate or severe dehydration in children, aged less than five years, with acute watery diarrhoea. On unconditional multiple logistic regression, 12 risk factors--infancy, minority religion, undernutrition, not washing hands by mother before preparation of food, frequency of stools > 8/day, frequency of vomiting > 2/day, measles in previous 6 months, withdrawal of breast-feeding/other feedings, withdrawal of fluids during diarrhoea, not giving oral rehydration solutions (ORS), home available fluids and both during diarrhoea--were significant. Based on regression coefficients, these factors were ascribed statistical weights of 5, 5, 4, 4, 22, 9, 11, 13, 5, 5, 5, and 7 respectively. The receiver-operating characteristic curve suggested a total score of 48 to be the best cut-off for predicting the development of moderate or severe dehydration. At this cut-off, the sensitivity, specificity, positive predictive value, Cohen's kappa, and overall predictive accuracy were 0.81, 0.81, 0.81, 0.61, and 0.86 respectively. If substantiated by further validation, this system can be used for predicting the development of dehydration at the earlier stage, thereby reducing the mortality associated with life-threatening dehydration.

Risk factors for development of dehydration in children aged under five who have acute watery diarrhoea: a case-control study.

OBJECTIVE: To identify factors for development of dehydration in under five year olds with acute watery diarrhoea. DESIGN: Hospital based unmatched case-control study. SETTING: Diarrhoea Treatment Unit, Government Medical College Hospital, Nagpur, India. PARTICIPANTS: The study included 387 cases of diarrhoea having severe or moderate dehydration and 387 controls suffering from diarrhea with mild or no dehydration. RISK FACTORS: The study included infancy, female sex, religion, residing in urban slums or rural area, under nutrition, cessation of breast feeding during diarrhoeal episode, fluid intake decrease/stopped during diarrhoea, ORS not received, home available funds (HAF) not received, both ORS and HAF not received, non-washing of hands by mother before preparation of food, after defaecation, after disposal of faeces, history of measles in the previous six months, frequency of stools > 8/d, frequency of vomiting more than twice per day and temperature more than 99 degrees F, as risk factors for development of dehydration. STATISTICAL ANALYSIS: Univariate analysis included OR, 95% CI for OR and Chi-square test. Multivariate analysis was carried out by unconditional multiple logistic regression (MLR). RESULTS: This study identified the significance of infancy, religion, severe undernutrition, non-washing of hands by mother before preparation of food, frequency of stool > 8/d, frequency of vomiting > 2/d, history of measles in previous six months, withdrawal of breast feeding during diarrhoea, withdrawal of fluids during diarrhoea and not giving ORS, HAF or both during diarrhoea, in the outcome of development of moderate or severe dehydration. CONCLUSIONS: Timely intervention in the preventable risk factors included in this study may prevent the development of moderate or severe dehydration in the children suffering form acute watery diarrhoea.

PIP: An unmatched case-control study conducted at the Diarrhea Treatment Unit of the Government Medical College Hospital in Nagpur, India, investigated risk factors for dehydration in 387 children under 5 years of age admitted with severe or moderate dehydration and 387 controls with no or mild dehydration. The presence of hypothesized risk factors for the development of moderate or severe dehydration in children with acute watery diarrhea was ascertained through interviews with the mothers. Multivariate analysis identified 12 significant risk factors: age under 12 months, Muslim religion, severe undernutrition, nonwashing of hands by the mother before food preparation, more than 8 stools per day, more than 2 vomiting episodes per day, a history of measles in the previous 6 months, withdrawal of breast-feeding during diarrhea, withdrawal of fluids during diarrhea, not giving home-available fluids during diarrhea, not giving oral rehydration solution (ORS) during diarrhea, and not giving both home-available fluids and ORS during diarrhea. These findings confirm the importance of continuing to supply breast milk, ORS, and other fluids to young children with watery diarrhea to prevent the development of life-threatening dehydration.

Peak expiratory flow rate in handloom weavers.

The present cross-sectional study with a comparison group was carried out to investigate peak expiratory flow rate (PEFR) in handloom weavers and to study relationship between reduction in PEFR with age, smoking, duration of cotton dust exposure and respiratory morbidity. This study include 319 handloom weavers and equal number of individuals (group matched for age and pair matched for sex) in comparison group. The decline in PEFR was significantly associated with advancing age, longer duration of exposure to cotton dust, tobacco smoking and presence of respiratory morbidity on univariate analysis, whereas on multivariate analysis longer duration of exposure to cotton dust and tobacco smoking was found to be non significant.

Self medication--a growing concern.

31% persons practiced self medication. They were more in 31-40 years (26.9%) and 41-50 years (30.8%). Males were more than females in self prescribers. Illiterate (23.1%) and graduates (26%) were more common self medicators, while labourers (26%) and business men (19.3%) were more involved in self medication. Fever (17.4%), cough (22.2%), boils (7.6%) and acidity (6.8%) were the common complaints for self-prescription. Thus analgesics and antipyretics, (30.9%), tonics (16.1) and antibiotics (10.7%) were commonly used drugs by the customers. Most of the information of drugs was from friends or neighbours (30.8%) or chemist (23.1%).

Late cutaneous syphilis.

Late cutaneous syphilis has become a rarity as a result of effective treatment of early and latent syphilis with antibiotics. Superficial nodular lesions of late cutaneous syphilis should be differentiated from conditions including sarcoidosis, leprosy, lupus vulgaris, and granuloma annulare. We report the case of a 50-year-old woman with superficial nodular lesions of late cutaneous syphilis.

Infant feeding practices in urban population--a clinic based study.

A clinic based cross-sectional study was conducted at Immunoprophylaxis Clinic at Govt. Medical College, Nagpur. Mothers of 217 children were interviewed for infant feeding practices. In 62.67% of children, breast-feeding was initiated within 24 hrs. after birth. About 22% mother used prelacteal feed and 70% mothers preferred demand feeding. Prominent area of concern includes discarding of colostrum, low exclusive breast feeding rate, delayed weaning and early termination of breast feeding. Further improvement in present day infant feeding practices is possible by emphasising on the health education component of existing nutritional programmes.

Breast-feeding practices in a tribal community of Melghat region in Maharastra State.

This cross sectional study was conducted at Chitta-Ranjan Das Mobile Hospital camp stationed at Dharni, to assess the current status of breast-feeding practices in a tribal community of Melghat region of Maharashtra State, using the key Breast-feeding indicators as recommended by W.H.O. working group on Infant Feeding in 1991. The tribal mothers of 462 children in the age group of 0-24 months were interviewed for breast-feeding practices. 69.69% of the children received their first breast feed after 24 hrs. of birth, however none of the children was breast fed within 2 hrs. of birth. The exclusive breast-feeding rate was 0.22 and the predominant breast-feeding rate was 0.79. Timely complementary feeding rate was 0.22. The continued breast-feeding rates at 1 year and 2 years were 0.88 and 0.64, respectively. The ever breast-fed rate, timely first-suckling rate and exclusive breast-feeding rate were 1.00, 0.00 and 0.22 respectively. The median duration of breast-feeding was 23 months. Hence this study confirms the traditional breast-feeding practices in Indian culture.

Infant feeding practices in a tribal community of Melghat region in Maharashtra state.

1. Out of 494 infants none was breastfed within 2 hours of delivery. 36% infants received first breastfeed after 24 hours of delivery 91.2% of the mothers used prelacteal feeds. 2. Only 31.06% of the infants were weaned, out of these only 7 received complementary foods between 4-6 months. 3. Thus, it can be concluded that though breastfeeding is practiced by all mothers, there is need for early initiation of breastfeeding and proper weaning habits.

PIP: The Chittaranjan Das Mobile Hospital Camp is affiliated with Government Medical College Hospital, Nagpur. 494 tribal mothers of infants attending the hospital camp stationed at Dharni, Amravati District between December 1993 and January 1994 were interviewed on their infant feeding practices. 251 male infants and 243 females were seen at the clinic. No child was breast fed within 2 hours of birth, 10.1% were breast fed within 3-6 hours of birth, and 36% were first breast fed after 24 hours of being born. Prelacteal feeds of honey water, jaggery water, sugar water, honeyghee, decoctions, and cow milk were used by 91.2% of mothers. 114 infants were weaned before age 1 year, of which only 7 (6.1%) were weaned at age 4-6 months, 50 (43.9%) at 7-9 months, and 57 (50%) at age 10-12 months. The following preparations were used for weaning: dal water in 26.3% of cases, dal rice in 21.1%, jawar roti in 20.2%, and cow milk 19.3% of the time.

Comparative evaluation of Butea frondosa and flurbiprofen for ocular anti-inflammatory activity in rabbits.

The roots and leaves of the plant Butea frondosa were evaluated for ocular anti-inflammatory activity on the subacute model of ocular inflammation in rabbits. The arkas (liquid preparations obtained by distillation of certain liquids or drugs soaked in water, using the Arka-Yantra or any other convenient modern distillation apparatus) were prepared using the roots and leaves of the plant. The arkas were formulated as gels using Pluronic F-127 (PF-127) 30% w/w as the polymer. The anti-inflammatory activity of the preparations were assessed by determining their effects on elevated intraocular pressure consequent to breakdown of blood/aqueous humour barrier. A commercial eyedrop of flurbiprofen 0.03% w/w was used to compare the ocular anti-inflammatory activity of the arkas of the plant. A marketed root arka was included in the study for comparison. The anti-inflammatory activity of the arkas formulated as gels were compared with flurbiprofen gel prepared using the same polymer. The changes in intraocular pressure were monitored at various time intervals after a single dose administration of the aqueous as well as gel formulations. In multiple dose studies the aqueous preparations were administered three times a day, while the gels were administered once a day up to day 30 and the intraocular pressure was monitored on different days post-administration. The findings reveal statistically significant differences (P < 0.05) between the arkas of the plant and the commercial eyedrop of flurbiprofen. The arkas of the plant proved to be better than the eyedrop of flurbiprofen, while with respect to gels, the intraocular pressure monitored at various time intervals revealed no statistically significant difference (P > 0.05) between the gel formulations. However, the changes in intraocular pressure monitored on different days post-administration until day 30, demonstrated that the gel produced from B. frondosa leaves arka was superior to all the other gels with respect to the extent of reduction of elevated intraocular pressure elicited experimentally.

Cyclopcidal activity of some new insect growth regulators.

A series of synthetic terpenoid diethers, with known mosquito development inhibitory activity, were tested for cyclopcidal activity against adult cyclops, Mesocyclops leuckarti. Four among these exhibited promising activity comparable to that of the conventional organophosphate, temephos, thus providing for the first time a possible reserve arsenal for the control of the guineaworm disease vector.