Sequence of reactions leading to cytochrome-p-450 synthesis-effect of drugs

The effect of phenobarbital on the rates of the synthesis of the protein and heme moieties of cytochrome P-450 has been studied. For this purpose, cytochrome P-450 has been partially purified as its P-420 derivative and the labeled amino acid incorporation into the protein has been studied after subjecting a partially purified preparation to sodium dodecyl sulfate gel electrophoresis. The incorporation studies into the protein species after sodium dodecyl sulfate gel electrophoresis reveal that the drug primarily accelerates the rate of apoprotein synthesis followed by an increase in the rate of heme synthesis. The messenger for apocytochrome P-450 appears to be fairly stable.

Infrared Spectroscopic Studies to Understand the Effect of Drugs at Molecular Level

In the recent past, there have been enormous efforts to understand effect of drugs on human body. Prior to understand the effect of drugs on human body most of the experiments are carried out on cells or model organisms. Here we present our study on the effect of chemotherapeutic drugs on cancer cells and the acetaminophen (APAP) induced hepatotoxicity in mouse model. Histone deacetylase inhibitors (HDIs) have attracted attention as potential drug molecules for the treatment of cancer. These are the chemotherapeutic drugs which have indirect mechanistic action against cancer cells via acting against histone deacetylases (HDAC). It has been known that different HDAC enzymes are over-expressed in various types of cancers for example; HDAC1 is over expressed in prostate, gastric and breast carcinomas. Therefore, in order to optimise chemotherapy, it is important to determine the efficacy of various classes of HDAC inhibitor drugs against variety of over-expressed HDAC enzymes. In the present study, FTIR microspectroscopy has been employed to predict the acetylation and propionylation brought in by HDIs. The liver plays an important role in cellular metabolism and is highly susceptible to drug toxicity. APAP which is an analgesic and antipyretic drug is extensively used for therapeutic purposes and has become the most common cause of acute liver failure (ALF). In the current study, we have focused to understand APAP induced hepatotoxicity using FTIR microspectroscopy. In the IR spectrum the bands corresponding to glycogen, ester group and were found to be suitable markers to predict liver injury at early time point (0.5hr) due to APAP both in tissue and serum in comparison to standard biochemical assays. Our studies show the potential of FTIR spectroscopy as a rapid, sensitive and non invasive detection technique for future clinical diagnosis.

Small intestine development of laying hens fed different fiber sources diets and crude protein levels

The objective of the presente study was to evaluate the effects on different dietary fiber sources and crude protein levels on the intestinal morphometry of commercial layers. Isa Brown® layers with 48 weeks of age were distributed in a completely randomized experimental design with a 3 x 2 + 1 factorial arrangement, resulting in seven treatments with seven replicates of eight birds each. At the end of the fourth experimental period (28 days each), birds were 64 weeks of age and were randomly chosen (two birds per replicate, totaling 14 birds per treatment), weighed and sacrificed by neck dislocation. Their intestine was dissected and the duodenum, jejunum and ileum were collected for subsequent analysis of intestinal morphometry. Treatments consisted of diets containing three different fiber sources (cottonseed hulls, soybean hulls or rice husks) and two crude protein levels (12% or 16%). Soybean hulls and 16% crude protein level promoted, in general, an increase in villus height and crypt depth in the three intestinal segments. In the duodenum, the control diet resulted in higher villus height and crypt depth relative to the diets containing fiber. In the jejunum, higher crypt depth values. In the ileum, dietary fiber increased villus height as compared to the control diet.

Effect of caloric restriction on myenteric neuroplasticity in the rat duodenum during aging

The objective of this study was to evaluate the effects of caloric restriction (CR) on myenteric neurons in the duodenum of Wistar rats during aging. Thirty rats were divided into three groups: the C group (six-month-old animals that were fed a normal diet from weaning until six months of age), the SR group (18-month-old animals that were fed a normal diet from weaning until 18 months of age) and the CR group (18-month-old animals that were fed a 30% CR diet after six months of age). After 12 months, the animals were euthanized. Whole-mount preparations of the duodenums were either stained with Giemsa or underwent NADPH-diaphorase histochemistry to determine the general myenteric neuron population and the nitrergic neuron subpopulation (NADPH-d +), respectively. The NADPH-d-negative (NADPH-d -) neuron population was estimated based on the difference between the Giemsa-stained and NADPH-d + neurons. The neurons were counted, and the cell body areas were measured. Aging was associated with neuronal loss in the SR group, which was minimized by caloric restriction in the CR group. The density (mm(2)) of the Giemsa-stained neurons was higher in the SR group (79.09 +/- 6.25) than in the CR (92.37 +/- 11.6) and C (111.68 +/- 15.26) groups. The density of the NADPH-d + neurons was higher in the SR group (44.90 +/- 5.88) than in the C (35.75 +/- 1.6) and RC (39.14 +/- 7.02) groups. The density of NADPH-d - neurons was higher in the CR (49.73 +/- 12.08) and C (75.64 +/- 17.05) groups than in the SR group (33.82 +/- 4.5). In the C group, 32% and 68% of the Giemsa-stained myenteric neurons were NADPH-d + or NADPH-d -, respectively. With aging (SR group), the percentage of nitrergic neurons (56.77%) increased, whereas the percentage of NADPH-d - neurons (43.22%) decreased. In the CR group, the change in the percentage of nitrergic (42.37%) and NADPH-d - (57.62%) neurons was lower. As NADPH-d - neurons will be mostly cholinergic neurons, CR appears to reduce the loss of cholinergic neurons during aging. The cell body dimensions (mu m(2)) were not altered by aging or CR. Thus. CR had a protective effect on myenteric neurons during aging. (C) 2012 Elsevier B.V. All rights reserved.

Surface area of the tip of the enterocytes in small intestine mucosa of broilers submitted to early feed restriction and supplemented with glutamine

A total of 640 one-day-old male Cobb chicks were used to evaluate the effects of early feed restriction and glutamine on villi density and tip surface of enterocytes in the small intestine of broilers. A two-factor factorial experimental design with glutamine and feed restriction as main factors was used. Treatments consisted of quantitative feed restriction at 30% of ad libitum intake from 7 to 14 days of age, and glutamine addition at 1% in the diet from 1 to 28 days of age. Sections of the small intestine (duodenum, jejunum, ileum) were collected at 14 and 21 days of age for analyses by scanning and transmission electron microscopy. Villi density decreased with age and increased in cranial-caudal direction. Glutamine increased villi density in the small intestine. Microvilli density and height decreased with age. Glutamine increased microvilli width. The jejunum was the segment with the largest surface area of the tip of the enterocytes, followed by the duodenum and the ileum. Feed restriction decreased the surface area of the tip of the enterocytes in the small intestine at 14 and at 21 days of age. Glutamine supplemented in the feed increased the surface area of the tip of the enterocytes of the jejunum and ileum at 21 days of age. © Asian Network for Scientific Information, 2007.

Ação do paracoxibe e/ou imipenem na cicatrização das anastomoses do intestino delgado e cólon de ratos: estudo biomecânico e anatomopatológico

Pós-graduação em Bases Gerais da Cirurgia - FMB

Effect of Time of Planting and Plant Size on the Productivity of ‘Festival’ and ‘Florida Fortuna’ Strawberry Plants in a Subtropical Environment

The effect of time of planting and plant size on the performance of ‘Festival’ and ‘Florida Fortuna’ strawberry (Fragaria ×ananassa) plants was studied at Nambour in southeastern Queensland, Australia, over 2 years. The main objective of the work was to determine whether small plants yielded proportionally less than large plants as planting was delayed. First, bare-rooted transplants of ‘Festival’ were divided into small (crown diameters ranging from 6 to 10 mm) or large plants (10 to 17 mm) and planted in late March, mid-April, or late April. Second, transplants of ‘Florida Fortuna’ were divided into small (5 to 8 mm) or large plants (8 to 17 mm) and planted in early April, mid-April, or early May. The early planting for each cultivar corresponded with the time that the transplants are first available from commercial strawberry nurseries. Yields were generally greater in plants planted in late March/early April compared with plants planted later. Differences in yield between the small and large plants were consistent across the different times of planting, with the small plants always having lower yields. Small transplants are an issue for the productivity of strawberry fields in this environment whether they are planted early or late. Producers should consider paying a premium for large transplants delivered early in the season.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

Effect of indomethacin on bile acid-phospholipid interactions: implication for small intestinal injury induced by nonsteroidal anti-inflammatory drugs.

The injurious effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the small intestine was not appreciated until the widespread use of capsule endoscopy. Animal studies found that NSAID-induced small intestinal injury depends on the ability of these drugs to be secreted into the bile. Because the individual toxicity of amphiphilic bile acids and NSAIDs directly correlates with their interactions with phospholipid membranes, we propose that the presence of both NSAIDs and bile acids alters their individual physicochemical properties and enhances the disruptive effect on cell membranes and overall cytotoxicity. We utilized in vitro gastric AGS and intestinal IEC-6 cells and found that combinations of bile acid, deoxycholic acid (DC), taurodeoxycholic acid, glycodeoxycholic acid, and the NSAID indomethacin (Indo) significantly increased cell plasma membrane permeability and became more cytotoxic than these agents alone. We confirmed this finding by measuring liposome permeability and intramembrane packing in synthetic model membranes exposed to DC, Indo, or combinations of both agents. By measuring physicochemical parameters, such as fluorescence resonance energy transfer and membrane surface charge, we found that Indo associated with phosphatidylcholine and promoted the molecular aggregation of DC and potential formation of larger and isolated bile acid complexes within either biomembranes or bile acid-lipid mixed micelles, which leads to membrane disruption. In this study, we demonstrated increased cytotoxicity of combinations of bile acid and NSAID and provided a molecular mechanism for the observed toxicity. This mechanism potentially contributes to the NSAID-induced injury in the small bowel.