Influence of non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine) on the pharmacodynamic activity of gliclazide in animal models

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes may occur as a result of HIV infection and/or its treatment. Gliclazide is a widely used drug for the treatment of type 2 diabetes. Efavirenz and nevirapine are widely used non-nucleoside reverse transcriptase inhibitors for the treatment of HIV infection. The role of Efavirenz and nevirapine on the pharmacodynamic activity of gliclazide is not currently known. The objective of this study was to examine the effect of oral administration of efavirenz and nevirapine on blood glucose and investigate their effect on the activity of gliclazide in rats (normal and diabetic) and rabbits to evaluate the safety and effectiveness of the combination.</p> <p>Methods</p> <p>Studies in normal and alloxan induced diabetic rats were conducted with oral doses of 2 mg/kg bd. wt. of gliclazide, 54 mg/kg bd. wt. of efavirenz or 18 mg/kg bd. wt. of nevirapine and their combination with adequate washout periods in between treatments. Studies in normal rabbits were conducted with 5.6 mg/1.5 kg bd. wt. of gliclazide, 42 mg/1.5 kg bd. wt. of efavirenz or 14 mg/1.5 kg bd. wt. of nevirapine and their combination given orally. Blood samples were collected at regular time intervals in rats from retro orbital puncture and by marginal ear vein puncture in rabbits. All the blood samples were analysed for blood glucose by GOD/POD method.</p> <p>Results</p> <p>Efavirenz and nevirapine alone have no significant effect on the blood glucose level in rats and rabbits. Gliclazide produced hypoglycaemic/antidiabetic activity in normal and diabetic rats with peak activity at 2 h and 8 h and hypoglycaemic activity in normal rabbits at 3 h. In combination, efavirenz reduced the effect of gliclazide in rats and rabbits, and the reduction was more significant with the single dose administration of efavirenz than multiple dose administration. In combination, nevirapine has no effect on the activity of gliclazide in rats and rabbits.</p> <p>Conclusion</p> <p>Thus, it can be concluded that the combination of efavirenz and gliclazide may need dose adjustment and care should be taken when the combination is prescribed for their clinical benefit in diabetic patients. The combination of nevirapine and gliclazide was safe. However, further studies are warranted.</p

Suicide risk in schizophrenia: learning from the past to change the future

Suicide is a major cause of death among patients with schizophrenia. Research indicates that at least 5–13% of schizophrenic patients die by suicide, and it is likely that the higher end of range is the most accurate estimate. There is almost total agreement that the schizophrenic patient who is more likely to commit suicide is young, male, white and never married, with good premorbid function, post-psychotic depression and a history of substance abuse and suicide attempts. Hopelessness, social isolation, hospitalization, deteriorating health after a high level of premorbid functioning, recent loss or rejection, limited external support, and family stress or instability are risk factors for suicide in patients with schizophrenia. Suicidal schizophrenics usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment. Awareness of illness has been reported as a major issue among suicidal schizophrenic patients, yet some researchers argue that insight into the illness does not increase suicide risk. Protective factors play also an important role in assessing suicide risk and should also be carefully evaluated. The neurobiological perspective offers a new approach for understanding self-destructive behavior among patients with schizophrenia and may improve the accuracy of screening schizophrenics for suicide. Although, there is general consensus on the risk factors, accurate knowledge as well as early recognition of patients at risk is still lacking in everyday clinical practice. Better knowledge may help clinicians and caretakers to implement preventive measures. This review paper is the results of a joint effort between researchers in the field of suicide in schizophrenia. Each expert provided a brief essay on one specific aspect of the problem. This is the first attempt to present a consensus report as well as the development of a set of guidelines for reducing suicide risk among schizophenia patients

Different vegetable crop rotations affect soil microbial communities and soilborne diseases of potato and onion: Literature review and a long-term field evaluation

A major concern in potato and onion production worldwide is the sustainability of crop production systems using short-term rotations. Although rotation crops are known to influence soil microbial communities, few long-term field studies have investigated effects of potato and onion crop rotations on soil microflora and soilborne diseases. A long-term trial (10 years) was established in New Zealand in the 2004–05 season to determine changes in soil characteristics, soil biological communities, plant productivity and soilborne diseases resulting from different crop rotations. Six different crop rotation ‘treatments’ were used: three were onion-focused and three were potato-focused. For both the onion- and potato-focused rotations, one treatment was continual monoculture, one was biennial alternating onion and potato (‘conventional’ rotation, common local commercial practice) and one was a 4-year cycle where the onion or potato crops were grown every fourth season with different crops in the intervening seasons (‘sustainable’ rotation). The results of the rotations were evaluated at the end of 2012–13, nine growing seasons after the trial began. Soils from the three potato-focused rotations had similar microbial biomass carbon (C) and nitrogen (N), total C and N, and enzyme activity, but had different microbial activity parameters. Soils from the three onion rotations differed in organic matter content, total C and N, enzyme activity and carbohydrate utilization. The main factor correlated with potato diseases (stem canker, black scurf) and crop yields was the amount of Rhizoctonia inoculum in the soil. Onion yields in 2012–13 were correlated with the severity of pink root during the growing season. Total microbial activity in soil gave better relationships to soilborne disease incidence (Rhizoctonia stem canker of potato or pink root of onion) and to crop yields, than soil chemical parameters (pH, nutrient status, C:N ratio) or other microbiological parameters (microbial biomass, total culturable bacteria and fungi, and microbial diversity). This research has broadened understanding of effects of crop rotations on soil microbial community characteristics, soilborne diseases and crop productivity of potatoes and onions grown in a soil and an area where intensive vegetable production is common. This knowledge will assist growers to increase crop yields and reduce soilborne pathogens in a sustainable manner. Based on the results from this study, intensive potato and onion production should require these crops to be grown within 4-year crop rotations in order to foster sustainable yields and minimize soilborne diseases

A long-term vegetable crop rotation study to determine effects on soil microbial communities and soilborne diseases of potato and onion

A rotation trial spanning nine consecutive growing seasons was established in 2004 to study cumulative effects of specific onion- and potato-focused crop rotations on soil nutrient levels, soil biological communities, plant productivity and soilborne diseases. Soil microbial activity, as determined by fluorescein diacetate hydrolysis, was greatest in the ‘sustainable’ potato rotation in five of the 6 years that the test was carried out. Rhizoctonia solani anastomosis group 3 DNA was first detected in potato monoculture soils in the fifth year, with numbers increasing from then on, but was not detected in the onion monoculture throughout the trial period. Potato yields were greater when a crop other than potato was grown in the previous year compared with when potatoes were the preceding crop. After 2005, mean annual onion yields from the onion monoculture were less than yields from the other rotations. Black scurf on potato tubers was the primary soilborne disease observed during the study, and the incidence of this disease was greater in the potato monoculture than the other rotations after the second year, and least when potatoes had not been grown in the same ground the three previous seasons. This long-term crop rotation study has demonstrated the benefits of a ‘sustainable’ rotation where potatoes or onions were grown every fourth growing season, with different crops (oat, broccoli, cabbage, squash) grown in the intervening years, compared with the conventional consecutive biennial crops of potato and onion

pH and water activity in culture media affect biological control activity of Trichoderma atroviride against Rhizoctonia solani

Biological control activity of Trichoderma spp. is heavily influenced by abiotic factors. Effects of pH and water activity (aw) in culture media of Trichoderma atroviride LU132 were assessed on conidium production, germination percentage and bioactivity against a soil-borne pathogen Rhizoctonia solani in dual agar culture assays. The effects of pH and buffer capacity in media were tested on T. atroviride colonies using different proportions (50, 100, 200 and 400mM) of phosphate buffers at pHs of 3.5, 4.5, 5.5, 6.5, 7.5 or 8.5. Water activity experiments tested different aw values (0.998, 0.995, 0.985, 0.977, 0.961 and 0.948). Conidium production was reduced with increasing phosphate buffer concentrations from 50 to 400mM. Maximum germination, and inhibition activity against R. solani was measured for conidia obtained from medium at pH 7.5. Greatest conidium production occurred at aw 0.995 and the least at aw 0.948. Mean conidium germination was greatest (78%) from media at aw 0.961, and least (21%) from aw 0.985. Inhibition and overgrowth activities of Trichoderma colonies were greatest at aw 0.961 and least at aw 0.998. This study has demonstrated that manipulation of culture conditions as such may improve conidium fitness (quantity and quality). However, these factors may not have caused independently effects on the fungus. Effects of physical growth conditions (besides nutritional requirements) are likely to be important for optimum production of biocontrol agents based on T. atroviride LU132, and other similar biocontrol agents

Nutrient amendments affect Trichoderma atroviride conidium production, germination and bioactivity

Trichoderma atroviride LU132, the active organism in two commercialised biological control products, was grown under different in vitro culture carbon to nitrogen ratios, to assess effects on conidium production, germination and bioactivity. Sucrose as a carbon source in agar-based growth media was adjusted to 4.2, 8.4, or 16.8. g/l carbon, and soy peptone as a nitrogen source to 0.03, 0.05, 0.11, 0.21, 0.42, 0.84, 1.68, or 3.36. g/l, to give C:N ratios in the growth media ranging from 5:1 to 160:1. Conidium production was greatest at 16.8. g/l carbon and least at 4.2. g/l, and was prolific at C:N 5:1, but was sparse at C:N 160:1. Mean conidium germination was greatest (68%) at 4.2. g/l carbon and least (58%) at 16.8. g/l carbon. Germination was greatest (74%) for C:N 5:1 and least (52%) for C:N 160:1. Trichoderma inhibition activity against the diseases-causing Rhizoctonia solani was also affected slightly for colonies obtained from conidia grown on media with 4.2. g/l carbon from 67% to 70% with 16.8. g/l carbon. Inhibition activity was greatest (73%) from conidia produced at C:N 5:1 and least (63%) from C:N 160:1. Low amounts of carbohydrate in growth media at C:N ratios near 5:1 were optimum for growth of T. atroviride LU132. Large amounts of carbohydrate probably repressed carbon catabolism, resulting in decreased conidium fitness. These results provide new knowledge to assist commercial production of biocontrol agents based on T. atroviride LU132

Biological fitness of Trichoderma atroviride during long-term storage, after production in different culture conditions

Identification of the production and storage factors that affect conidium germination and bioactivity (fitness) will assist the success of biological control agents. Effects of culturing conditions on conidium fitness of Trichoderma atroviride LU132 were examined in different storage conditions over time. Abiotic factors (temperature, nutrients, water activity and pH) during production were studied. Conidia from the culturing regimes which resulted in greatest and least bioactivity against Rhizoctonia solani in dual culture were selected to assess effects of storage conditions on conidium fitness. Fitness of the test conidia was examined after storage at 30°C and at 0% or 50% relative humidity (RH) over 6 months. Fitness declined over time, and the decline was greater for 50% RH than 0% RH, probably through reduced metabolic activity of conidia during long-term storage. Stored conidia were probably affected by dehydration, temperature and other factors such as oxidation, before and during storage, and also by rehydration after storage. The greatest number of conidia and germination percentage resulted from production at 25°C, but greatest bioactivity resulted from those produced at 30°C. No significant effects on bioactivity were detected between the conidium production treatments C : N 5 : 1 and C : N 160 : 1, indicating that C : N ratio in culture medium is not important for conidium survival of T. atroviride