Simulating adaptation strategies to offset potential impacts of climate variability and change on maize yields in Embu County, Kenya.

In this study, we assessed the possible impacts of climate variability and change on growth and performance of maize using multi-climate, multi-crop model approaches built on Agricultural Model Intercomparison and Improvement Project (AgMIP) protocols in five different agro-ecological zones (AEZs) of Embu County in Kenya and under different management systems. Adaptation strategies were developed that are locally relevant by identifying a set of technologies that help to offset potential impacts of climate change on maize yields. Impacts and adaptation options were evaluated using projections by 20 Coupled Model Intercomparison Project-Phase 5 (CMIP5) climate models under two representative concentration pathways (RCPs) 4.5 and 8.5. Two widely used crop simulation models, Agricultural Production Systems Simulator (APSIM) and Decision Support System for Agrotechnology Transfer (DSSAT) was used to simulate the potential impacts of climate change on maize. Results showed that 20 CMIP5 models are consistent in their projections of increased surface temperatures with different magnitude. Projections by HadGEM2-CC, HadGEM2-ES, and MIROC-ESM tend to be higher than the rest of 17 CMIP5 climate models under both emission scenarios. The projected increase in minimum temperature (Tmin) which ranged between 2.7 and 5.8°C is higher than the increase in maximum temperature (Tmax) that varied between 2.2 and 4.8°C by end century under RCP 8.5. Future projections in rainfall are less certain with high variability projections by GFDL-ESM2G, MIROC5, and NorESM1-M suggest 8 to 25% decline in rainfall, while CanESM2, IPSL-CM5A-MR and BNU-ESM suggested more than 85% increase in rainfall under RCP 8.5 by end of 21st century. Impacts of current and future climatic conditions on maize yields varied depending on the AEZs, soil type, crop management and climate change scenario. Impacts are largely negative in the low potential AEZs such as Lower Midlands (LM4 and LM5) compared with the high potential AEZs Upper Midlands (UM2 and UM3). However, impacts of climate change are largely positive across all AEZs and management conditions when CO2 fertilization is included. Using the differential impacts of climate change, a strategy to adapt maize cultivation to climate change in all the five AEZs was identified by consolidating those practices that contributed to increased yields under climate change. We consider this approach as more appropriate to identify operational adaptation strategies using readily available technologies that contribute positively under both current and future climatic conditions. This approach when adopted in strategic manner will also contribute to further strengthen the development of adaptation strategies at national and local levels. The methods and tools validated and applied in this assessment allowed estimating possible impacts of climate change and adaptation strategies which can provide valuable insights and guidance for adaptation planning.

Association of progesterone receptor gene polymorphism (PROGINS) with endometriosis, uterine fibroids and breast cancer.

Endometriosis, uterine fibroids and breast cancer are female health disorders associated with a great deal of morbidity. Since all these disorders are hormone responsive, our present study has been carried out to identify the association of 306bp Alu insertion polymorphism in intron 7 of progesterone receptor gene (PROGINS). DNA was isolated from the blood samples of 445 Asian Indian women, which included 100 endometriosis, 80 fibroids and 157 cases of breast cancer along with 108 age matched normal healthy women as controls. PROGINS polymorphism was assessed by PCR followed by agarose gel electrophoresis. Results showed that T2 allele frequency is 5%, 10% and 14.6% in endometriosis, uterine fibroids and breast cancer, as compared to 5.5% in controls. This indicates that PROGINS can be considered as a predisposing risk marker for breast cancer but not for endometriosis and uterine fibroids.

The genotoxic and cytotoxic effects of ribavirin in rat bone marrow.

The genotoxic and cytotoxic effects of the antiviral drug, ribavirin, was studied in rat bone marrow by employing the micronucleus assay. Ribavirin in doses of 10, 15, 20, 30, 50, 75, 100 and 200 mg/kg, and cyclophosphamide (CP) 40 mg/kg (only for sex-difference study) were injected intraperitoneally. Bone marrow was collected at 24 h and 48 h following the injection. To evaluate the recovery, the bone marrow was also sampled at 72 h from 20, 100 and 200 mg/kg treated rats. The micronucleus assay was conducted according to the standard procedure. Ribavirin elevated the incidence of micronuclei (except 10 mg/kg) in erythrocytes (P<0.01). The micronucleated polychromatic erythrocytes showed the initial steep increase at 15 and 20 mg/kg dose level, then with the gradual increase, possibly due to the limited metabolism and action of higher doses. The incidence of micronucleated normochromatic erythrocytes was not dose dependent. The effect was more at 48 h than 24 h due to prolonged toxicity of the drug or its metabolites, and by 72 h, recovery was observed even though the genotoxicity was significant. The PCE% decreased as the dose was increased up to 75 mg/kg, then without much difference between two higher doses. Only 100 mg/kg ribavirin and CP showed more toxicity on male rats. Cytotoxicity was seen due to hindered erythropoiesis or cell destruction. Our findings suggest that ribavirin is genotoxic and cytotoxic agent for rat bone marrow.

Effect of ribavirin on epididymal sperm count in rat.

Ribavirin (1-beta-D-ribofuranosyl-1, 2, 4-triazole-3-Carboxamide) is a potent inhibitor of inosine monophosphate dehydrogenase, used widely as an antiviral drug. Although it has been reported as a teratogen, its effect on spermatogenesis is not known. Male Wistar rats were segregated into 24 groups of 5 in each. Six groups were treated with water, 6 groups with 20 mg/kg, another 6 groups with 100 mg/kg and remaining 6 groups with 200 mg/kg for 5 days at intervals of 24 h (i.p.). Animals were anaesthetized at 14, 28, 35, 42, 70 and 105 days following the last exposure, laparatomy was conducted, epididymis was removed, minced in 1 ml phosphate buffered saline (PBS, pH 7.2), filtered and stained with 1% aqueous eosin Y. An aliquot was taken in haemocytometer, diluted in PBS and charged into Neubauer's chamber. Spermatozoa were counted in 8 squares except the central, and multiplied by 5 x 10(4). Data were analysed by Mann-Whitney "U" test. Ribavirin significantly decreased the sperm count in a dose and time dependent pattern and showed a recovery by day 105 except at 200 mg/kg. Ribavirin is reversibly cytotoxic to germ cells and decreases the production of spermatozoa.

Ribavirin-induced sperm shape abnormalities in Wistar rat.

Ribavirin (1-beta-D-ribofuranosyl-1,2,4, triazole-3 carboxamide) is a broad-spectrum antiviral drug. This study was aimed to investigate the mutagenicity of ribavirin on germ cells by employing sperm morphology assay. Male Wistar rats were treated with water, cyclophosphamide (CP) 40 mg/kg, and ribavirin 20, 100 and 200 mg/kg (i.p.) for 5 consecutive days at intervals of 24h. Following the last exposure, at 14, 28, 35, 42 and 70 days, the epididymal sperm smears were obtained and stained according to the standard procedure. One thousand sperms per animal were classified into normal and different abnormal types. Both CP and ribavirin-induced anomalies of head and tail of sperm except at 70 days. In CP groups, maximum incidence was observed at 28, 35 and 42 days. Ribavirin 20 mg/kg induced maximum incidence at 14 and 42 days, 100 mg/kg at 28 and 42 days and 200 mg/kg at 28-42 days. These results show that ribavirin is mutagenic to rat germ cells in a transient fashion.

Collagen-chitosan polymeric scaffolds for the in vitro culture of human epidermoid carcinoma cells.

A biodegradable polymer scaffold was developed using collagen and chitosan, in the form of interpenetrating polymeric network (IPN), for in vitro culture of human epidermoid carcinoma cells (HEp-2, Cincinnati). Glutaraldehyde was used as cross-linking agent for the development of scaffold. Various types of scaffolds were prepared using different proportionate mixtures of collagen and chitosan solutions in the ratio of 3:7, 4:6, 5:5, 6:4 and 7:3 (collagen:chitosan). These scaffolds were fully characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA). Equilibrium swelling studies were carried out in phosphate buffer of physiological pH (7.4) to study its swelling characteristics at slightly alkaline pH. The scaffold that showed optimum swelling property was selected as the best scaffold for performing in vitro culture studies. In vitro culture studies were carried out using HEp-2 cells, over the selected scaffold and its growth morphology was determined through optical photographs taken at different magnifications at various days of culture. The results of the above studies suggest that the scaffolds prepared from collagen and chitosan can be utilized as a substrate to culture HEp-2 cells and can also be used as an in vitro model to test anticancerous drugs.

Controlled release of lysozyme from succinylated gelatin microspheres.

Gelatin was anionized to increase the carboxylic acid groups through succinylation. Succinylation of gelatin was performed using varying amounts of succinic anhydride. This gave various percentages of substitution. Lysozyme, a cationic antibacterial enzyme, which has important applications in the reduction of prosthetic valve endocarditis, was chosen as a model protein drug. Microspheres were prepared using unmodified gelatin and succinylated gelatin (SG) and lysozyme was incorporated into them. The percentage loading and release profiles of lysozyme for gelatin and SG microspheres were evaluated and compared. It was found that the SG microspheres exhibited higher loading efficiency for lysozyme (50%) than the unmodified gelatin microspheres. The in vitro release of lysozyme from SG microspheres occurred up to 122 h, compared to 96 h for gelatin microspheres, for the release of most of the lysozyme incorporated. This prolonged release of lysozyme from SG microspheres was attributed to the electrostatic interaction between the cationic lysozyme and the anionic SG microsphere carrier.

5-fluorouracil (5-FU) induces the formation of giant cells and sloughing of seminiferous epithelium in the rat testis.

The chemotherapeutic agent, 5-fluorouracil (5-FU) has been widely used in the treatment of a variety of cancers. Its effect on the testis has not been substantially studied. Present study was conducted to evaluate the gonadotoxicity of 5-FU in male albino rats. Animals were injected with single dose of 5-FU (10, 50 and 100 mg/kg, i.p.) and sampled on 1, 3, 15 and 30 day post exposure. Animals were anaesthetised, testes were perfusion fixed by Bouin's fluid. Five micron thick paraffin sections were stained with haematoxylin and eosin. Slides were screened for the incidence of partially and extensively sloughed tubules. Data were analysed by Mann Whitney 'U' test. Only 100 mg/kg induced multinucleated cells on 3rd day. All doses of 5-FU induced sloughing of the seminiferous epithelium. Maximum number of partially sloughed tubules were seen on third day. Partial sloughing was not dose dependent except on 15th day. The extensive sloughing was dose dependent except on 30th day. The result indicates that all the doses of 5-FU tested in this study cause sloughing of epithelium and only 100 mg/kg induces the formation of giant cells on third day.

Reduction of calcification by various treatments in cardiac valves.

The importance of glutaraldehyde pretreated bioprosthetic heart valves fabricated from bovine pericardium or porcine aortic valves is well realized in the management of valvular heart diseases. But, calcification limits the durability and is the most frequent cause of failure of these bioprosthetic heart valves. Various research groups in the world are actively involved in describing, understanding, and preventing calcification of bioprosthetic heart valves. Since there is no satisfactory clinical means for preventing or treating this disorder, attempts are made to improve the anticalcification properties of the replacement valves in the preparation stage itself. Research in this area is very active, and many newer approaches are made to mitigate the problem. An attempt has been made in the present article to review various theories put forward to explain the causative factors involved and mechanistic aspects of biocalcification and to present various strategies attempted for the prevention of calcification with the special feature on the work done in the area in our laboratory.

Transrectal ultrasonography versus computed tomography in staging rectal carcinoma.

BACKGROUND: Since therapy of rectal carcinoma depends on the extent of disease, staging becomes important. AIM: To assess the ability of transrectal ultrasonography (TRUS) and computed tomography (CT) to stage rectal carcinoma. METHODS: Ten patients with rectal carcinoma were examined by TRUS and plain and contrast-enhanced CT scan; their findings were compared with each other and with those at surgery. RESULTS: TRUS identified wall invasion in all ten cases and perirectal fat infiltration in all five cases in whom these were present. Node involvement was detected in five cases on TRUS and two of six cases on CT. Metastasis to bladder (one case) was not recognized by TRUS but was seen on CT. CONCLUSION: TRUS is inexpensive and superior to CT in staging early rectal carcinoma; limited depth of penetration is its major limitation. CT is useful for the diagnosis of advanced disease.

New treatments using alginate in order to reduce the calcification of bovine bioprosthetic heart valve tissue.

Calcification limits the functional lifetime of cardiac valve substitutes fabricated from glutaraldehyde preserved bovine pericardium. Host factors, mainly younger age, and implant factors, mainly glutaraldehyde cross-linking, are implicated in the calcification process. Glutaraldehyde cross-linking is believed to activate the potential sites in the tissues for biocalcification. In the present work, we investigated the possibility of using alginate azide (AA) instead of glutaraldehyde for the preservation of pericardial tissues in order to enhance the durability of bioprosthetic heart valves. Grafting with poly(GMA-BA) copolymer to the alginate azide cross-linked pericardial (AACPC) tissue was carried out to obtain better stability, strength, and anticalcification properties. The strength property and thermal stability of the AA cross-linked tissues were studied. Calcification studies in rat subdermal models reveal that AA cross-linking reduces the calcification to negligible levels. After 30 days implantation, the calcium content was found to be 10.4 +/- 1.2 and 6.1 +/- 0.3 micrograms mg-1 for untreated AACPC and polymer grafted AACPC, respectively, compared to a value of 100 +/- 1.2 micrograms mg-1 calcium recorded for control glutaraldehyde cross-linked pericardial (GCPC) tissues.

Immunoglobulin and C3-activator profile of the microbiology laboratory worker.

The levels of immunoglobulin, C3-Activator and C3c in the sera of members of staff who have been continuously engaged for upwards of 10 years in the microbiological routine laboratory of a teachings hospital were determined. These were compared with the local normals, with those of the junior members of staff in the same laboratory but who had put in less than 5 years continuous service and with a control group. The means in all five determinations were much higher in the senior members of staff than the normal standards of the area, particularly the IgG, which was almost double the local normals. The levels for the junior staff were on the whole slightly higher than the control group. The increase in the levels of immunoglobulins with corresponding increases in C3-Activator and 3Cc suggest that immunological reactions, with the binding of complement in the alternate and classical pathways of activation are taking place in most of these senior workers. In the absence of any manifest illness in the senior staff, the findings may suggest a high degree of immunological protection.

Development of hydroxyapatite derived from Indian coral.

A simple method of converting the calcium carbonate skeleton of the corals available in the Indian coast into hydroxyapatite granules has been developed. By heating the coral to 900 degrees C, the organic materials were eliminated. Powder X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) were employed to characterize the coral and to optimize the processing parameters as well as to confirm the hydroxyapatite formation. The coral used exhibits the presence of both aragonite and calcite phases (dimorphism). At a temperature of 900 degrees C the coral was found to decompose all the carbonate phases. The pre-heated coral is converted into hydroxyapatite by a chemical exchange reaction with di-ammonium phosphate under hydrothermal conditions. The hydroxyapatite obtained was in powder form and does not contain any impurities. The in vitro solubility test of the apatite granules performed in Gomoris, Michalelis, Sorensens, Ringer's and phosphate buffer of pH 7.2 and de-ionized water indicated the stability of the coralline hydroxyapatite.

Rate-controlling biopolymer membranes as transdermal delivery systems for nifedipine: development and in vitro evaluations.

Membrane permeation-controlled transdermal delivery devices for the controlled delivery of nifedipine were developed using collagen (which was extracted from calf fetus skin) and chitosan membranes as rate-controlling membrane. To increase the stability of nifedipine in the systems, alginate gel was used as drug reservoir. Transdermal devices were fabricated by adhesive sealing techniques. In vitro drug release studies were carried out using modified Franz diffusion cells. Drug release was found to depend on the type of membrane used to control the drug delivery, suggesting that drug delivery is efficiently controlled by the rate-controlling membranes.

Azo polymeric hydrogels for colon targeted drug delivery.

Azo polymeric hydrogels were developed for colon specific targeting. Methacryloyloxy azobenzene was synthesized and hydrogels were prepared by copolymerizing with hydroxyethyl methacrylate. These hydrogels were characterized by various spectral techniques such as Fourier transform infrared spectroscopy, thermogravimetric analysis and scanning electron microscopy. Equilibrium swelling measurements of the hydrogels were carried out in distilled water and also in simulated gastric and intestinal fluids. The in vitro release studies of the incorporated 5-flurouracil were carried out in simulated gastric and intestinal fluids. The in vitro release profiles of the drug were also obtained in the presence of azoreductase in the culture of intestinal flora. The release was faster and almost followed a zero order pattern. This can be attributed to the cleavage of the azo crosslinks in the hydrogel by the azoreductase and the release of the entrapped drug at the site of targeting i.e., colon.

Neuroticism and stressful life events in patients with non-ulcer dyspepsia.

Hindi adaptation of the Middlesex Hospital Questionnaire (MHQ), Brief Psychiatric Rating Scale and Presumptive Stressful Life Events Scale were used to measure neuroticism, psychiatric morbidity and stressful life events in 35 patients with non-ulcer dyspepsia (NUD), 22 cass of peptic ulcer disease (PUD), 65 irritable bowel syndrome (IBS) and 45 age and sex matched healthy controls. NUD subjects had significantly higher total MHQ scores (28.8 +/- 11.3; p < 0.001) and scores in subscales of somatization (7.8 +/- 3.4; p < 0.001) and hysterical personality traits (5.5 +/- 2.8; p < 0.01) compared to healthy controls. MHQ scores in IBS subjects was significantly higher than in NUD, but in PUD subjects it was in-between NUD and healthy controls. Psychiatric morbidity, as assessed by Brief Psychiatric Rating Scale, was significantly higher in patients with NUD and IBS than in normal controls. Stressful Life event score was statistically similar in all the groups.

Development and in vitro evaluation of chitosan-based transdermal drug delivery systems for the controlled delivery of propranolol hydrochloride.

Membrane permeation-controlled transdermal drug delivery systems were prepared using the natural polymer, chitosan. An adhesive sealing technique was used to construct the devices. Propranolol hydrochloride was selected as the model drug for the present study. Chitosan membranes with different permeability to propranolol hydrochloride obtained by controlled cross-linking with glutaraldehyde were used to regulate the drug release in the devices. Chitosan gel was used as the drug reservoir. The ability of these devices to deliver the drug while supported on rabbit pinna skin was tested by conducting in vitro studies in modified Franz diffusion cells. The drug release profiles showed that the drug delivery is completely controlled by the devices. The rate of drug release was found to be dependent on the type of membrane used.

Recent developments of collagen-based materials for medical applications and drug delivery systems.

In this review, an attempt was made to summarize some of the recent developments in the application of collagen as a biomaterial and in drug delivery systems. The main applications covered include: collagen for burn/wound cover dressings; osteogenic and bone filling materials; antithrombogenic surfaces; and immobilization of therapeutic enzymes. Recently, collagen used as a carrier for drug delivery has attracted many researchers throughout the world. The use of collagen for various drug delivery systems has also been reviewed in this article. Collagen-based drug delivery systems include: injectable microspheres based on gelatin (degraded form of collagen); implantable collagen-synthetic polymer hydrogels; interpenetrating networks of collagen; and synthetic polymers collagen membranes for ophthalmic delivery. Recent efforts to use collagen-liposomal composites for controlled drug delivery, as well as collagen as controlling membranes for transdermal delivery, were also reviewed. In this review, the main emphasis was on the work done in our laboratory.

Polymer-coated gelatin capsules as oral delivery devices and their gastrointestinal tract behaviour in humans.

In oral delivery of protein and peptide drugs there is a great need for suitable devices for delivering the therapeutic agent-incorporated microspheres selectively in the intestine. It is essential that the drug-loaded multiple unit carrier system should be protected from the harsh environment of the stomach and deliver the carrier system in the large intestine where drug action or absorption is desired. Gelatin capsules were coated with various concentrations of sodium alginate and cross-linked with appropriate concentrations of calcium chloride and tested in vitro for resistance to gastric and intestinal medium. Gelatin capsules coated with 20% w/v of the polymer which gave the most promising result in vitro were evaluated in human volunteers for their in vivo gastro intestinal tract behaviour. The radiographical studies show that while the uncoated gelatin capsules disintegrated in the stomach within 15 min of ingestion, the alginate coated gelatin capsules remained intact as long as they were retained in the stomach (up to 3 h) and then migrated to the ileocecal region of the intestine and disintegrated.