Quinolone-resistant typhoid fever.
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Adult↗
Biomedical subjects
P Khosla
Publications and source records attributed to P Khosla.
Effect of garlic oil on ethanol induced gastric ulcers in rats.
Garlic oil was evaluated for gastroprotective activity against ethanol induced ulcers. Reactive oxygen species are involved in the pathogenesis of these ulcers. The possible involvement of garlic oil in restraining the oxidation process produced in gastric tissue was also investigated. The ulcer index, lipid peroxidation and antioxidant enzyme activity (GPx, catalase, SOD) were determined. Pretreatment with garlic oil in doses of 0.25 and 0.5 mg/kg, 30 min before administration of ethanol (1 mL of 100%) caused a decrease in ulcer index and lipid peroxidation and ameliorated the decrease in antioxidant enzyme levels caused by ethanol. The result suggests that garlic oil possesses antioxidant properties and provides protection against ethanol induced gastric injury.
Animals↗
Novel short-term effects of adenovirus Ad-36 on hamster lipoproteins.
OBJECTIVE: Human adenovirus Ad-36 induces adiposity and lowers total serum cholesterol in chickens, mice and marmosets and Ad-36 antibodies are associated with human obesity. We examined the early effects of Ad-36 inoculation on plasma cholesterol levels in hamsters fed a hyperlipidemic diet. DESIGN: A total of 32 male Golden Syrian hamsters were divided into two equal weight-matched groups and intranasally inoculated with Ad-36 (INF: infected) or media (CON: control). In each group, the animals were fed either a purified diet (PF, n=8) 40%en fat +/-194 mg cholesterol/1000 kcal or chow (C, n=8) ad libitum. Animals were killed 5 weeks postinoculation. RESULTS: Nested PCR assay detected Ad-36 DNA in the lung, liver, visceral adipose tissue and skeletal muscle of the INF group, but not in the CON animals. Ad-36 antibodies were detected in the INF group only. For all animals, total plasma cholesterol (TC) was not significantly affected by Ad-36 treatment (203+/-92 vs 193+/-75 mg/dl, P=NS; INF vs CON, respectively). In 5 weeks, Ad-36 infection had no effect on TC concentration in hamsters fed chow (128+/-39 vs 130+/-27 mg/dl, INF-C vs CON-C, respectively) or those fed PF (269+/-70 vs 256+/-47 mg/dl, INF-P vs CON-P, respectively). However, lipoproteins isolated by density gradient ultracentrifugation showed a greater proportion of LDL cholesterol in INF animals, as compared to CON (28.4+/-1.6% vs 16.4+/-1.2%, P=0.02), regardless of dietary treatment (INF-P vs CON-P: 27.3+/-2.1 vs 15.7+/-1.5%, P=0.07; and INF-C vs CON-C: 29.4+/-1.2 vs 17.0+/-1.1%, P=0.009). This shift appears to be from HDL cholesterol to the LDL fractions. CONCLUSION: These data suggest that in the hamster (a model resembling several aspects of human lipoprotein metabolism), Ad-36 infection may acutely affect the intravascular processing of lipoproteins resulting in a more atherogenic lipoprotein profile.
Adenoviridae Infections↗
Prevalence of risk factors to coronary heart disease in an Arab-American population in southeast Michigan.
Although significant advances have been made in the area of cardiovascular disease, few studies have targeted ethnic groups. There is a large and growing Arab-American (AA) population living in Southeast Michigan, whose risk of cardiovascular disease may be on the increase. The objective of this study was to evaluate the prevalence of cardiovascular disease risk factors and associated behavioral factors in an AA community with a large population of emigrants, subjected to significant lifestyle changes. Three hundred and fifty-two AA living in Southeast Michigan, mostly from the Middle East, were screened to determine their eating and smoking habits, body mass index (BMI) body fat analysis, blood pressure, and complete lipid profiling. Overweight was defined as a BMI greater than or equal to the 85th percentile value for age- and sex-specific reference data from the third National Health and Nutrition Examination Survey (NHANES III). Correlation analysis was used to examine factors associated with being overweight, with adjustment for age and sex. Blood cholesterol concentrations were compared with published data for Arabs from the Middle Eastern countries. The overall prevalence of being overweight in subjects aged 35 and older was significantly higher than NHANES III reference data (Men, 27.7% (95% confidence interval, 21.8-34.5); women, 33.7% (95% confidence interval, 27.9-40.1)). A mean cholesterol concentration of 210 +/- 4 mg/dl was observed in those over the age of 40. The mean high-density lipoprotein (HDL)-cholesterol levels for men and women were 38 and 48 mg/dl, respectively. Greater than 54.6% of all subjects had a total cholesterol:HDL ratio > 4.5. Although being overweight and obesity were prevalent in this population, the mean BMI for men was 25.7 +/- 0.34, compared with 27 +/- 0.58 for women. Increased BMI was significantly correlated (P < 0.01) with increased blood pressure, increased glucose levels, increased total cholesterol and decreased HDL-cholesterol levels (P < 0.01). Elevation in risk factors to cardiovascular disease is prevalent in this population and indicates a need for programs targeting primary prevention of obesity in men and women. These results, which could be attributed in part to lifestyle changes typical of most emigrant populations, suggest an increase in the risk for developing cardiovascular disease. In addition, this study provides a basis for future intervention to improve the health of this population.
Adult↗
A study of cardiovascular effects of Azadirachta indica (neem) on isolated perfused heart preparations.
The effects of aqueous leaf extract of Azadirachta indica were evaluated on isolated prefused frog and rabbit heart. Dose dependent negative inotropic and chronotropic effects were observed in both the heart preparation. An increase in coronary blood flow in isolated rabbit heart was observed. The effects were not blocked by atropine and mepyramine in both the preparations. The data suggests that A. indica could be of benefit in coronary artery disease and arrhythmias.
Animals↗
Palmitic and stearic acids similarly affect plasma lipoprotein metabolism in cynomolgus monkeys fed diets with adequate levels of linoleic acid.
This study was designed to evaluate whether the exchange of specific saturated fatty acids [SFA; palmitic acid (16:0) for stearic acid (18:0)] would differentially affect plasma lipids and lipoproteins, when diets contained the currently recommended levels of total SFA, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA). Ten male cynomolgus monkeys were fed one of two purified diets (using a cross-over design) enriched either in 16:0 (palmitic acid diet) or 18:0 (stearic acid diet). Both diets provided 30% of energy as fat (SFA/monounsaturated fatty acid/PUFA: 1/1/1). The palmitic acid and stearic acid diets were based on palm oil or cocoa butter (59% and 50% of the total fat, respectively). By adding different amounts of sunflower, safflower and olive oils, an effective exchange of 16:0 for 18:0 of approximately 5% of energy was achieved with all other fatty acids being held constant. Monkeys were rotated through two 10-wk feeding periods, during which time plasma lipids and in vivo lipoprotein metabolism (following the simultaneous injection of (131)I-LDL and (125)I- HDL were evaluated). Plasma triacyglycerol (0.40 +/- 0.03 vs. 0.37 +/- 0.03 mmol/L), plasma total cholesterol (3.59 +/- 0.18 vs. 3.39 +/- 0.23 mmol/L), HDL cholesterol (1.60 +/- 0.16 vs 1.53 +/- 0.16 mmol/L) and non-HDL cholesterol (2.02 +/- 0.26 vs. 1.86 +/- 0.23 mmol/L) concentrations did not differ when monkeys consumed the palmitic acid and stearic acid diets, respectively. Plasma lipoprotein compositional analyses revealed a higher cholesteryl ester content in the VLDL fraction isolated after consumption of the stearic acid diet (P < 0.10), as well as a larger VLDL particle diameter (16.3 +/- 1.7 nm vs. 13.8 +/- 3.6 nm; P < 0.05). Kinetic analyses revealed no significant differences in LDL or HDL transport parameters. These data suggest that when incorporated into diets following current guidelines, containing adequate PUFA, an exchange of 16:0 for 18:0, representing approximately 11 g/(d.10.46 mJ) [ approximately 11 g/(d.2500 kcal)] does not affect the plasma lipid profile and has minor effects on lipoprotein composition. Whether a similar effect would occur in humans under comparable dietary conditions remains to be established.
Animals↗
Conjugated linoleic acid: effects on plasma lipids and cardiovascular function.
Conjugated linoleic acid is a collective name for mixtures of several positional and geometric conjugated dienoic isomers of linoleic acid, which have been shown to impact favorably on several biological processes, particularly carcinogenesis. Recent studies have clearly established that the c9, t11 and t10, c12 isomers have distinct biological effects. The latter may be of particular importance in affecting blood lipids. Because conjugated linoleic acid has been suggested to be anti-atherogenic, this review is focused on its effects on cardiovascular function. Careful scrutiny of the literature suggests that at present it is premature to assign any beneficial role to conjugated linoleic acid in terms of its ability to impact either blood lipids or atherogenesis.
Animals↗
Effects of exchanging 4%en between dietary stearic and palmitic acid on hamster plasma lipoprotein metabolism.
This study was designed to determine whether the exchange of specific fatty acids (palmitic (16:0) for stearic (18:0)), would exert differential effects on plasma and lipoprotein lipids, when diets contained approximately 30%en from fat with adequate levels of linoleic acid (18:2). Thirty-two male Golden Syrian hamsters were fed isocaloric purified diets with comparable amounts of 18:2 (approximately 10.5%en). The 18:0-rich diet (50% cocoa butter, 41% safflower oil, 9% sunflower oil) provided 4.8%en 16:0 and 5.3%en from 18:0, while the 16:0-rich diet (59% palm oil, 36% safflower oil, 5% olive oil) provided 8.7%en from 16:0 and 1.2%en from 18:0, resulting in a 16:0/18:0 exchange of approximately 4%en. Both diets contained negligible amounts of lauric and myristic acid (< 0.2%en), approximately 9.5%en from oleic acid and 77 mg cholesterol/1000 kcal. Animals were fed their respective diets for 4 weeks at which point various lipid and lipoprotein parameters were measured. There were no significant difference between dietary groups for any of the measured parameters, which included body weights, food consumption, plasma lipids, lipoprotein lipid and apoprotein concentrations, as well as lipoprotein compositions. Additionally, estimated diameters of various lipoprotein particles were not affected by the fatty acid exchanges employed. Thus these data suggest that when total fat is restricted to 30%en and 18:2 levels are approximately 10%en, a 4%en exchange between 16:0 and 18:0 (representing intakes of approximately 9 g/d/2000 kcal diet) produces comparable plasma lipids.
Animals↗
Pork fat and chicken fat similarly affect plasma lipoprotein metabolism in cynomolgus monkeys fed diets with adequate levels of linoleic acid.
The effects on plasma lipoprotein metabolism of replacing pork fat (PF) with chicken fat (CF) (formulated as part of currently recommended prudent diets) was evaluated in 10 male cynomolgus monkeys. Monkeys were rotated through three dietary periods, (each of 10-wk duration), during which total cholesterol (TC), triacylglycerol (TG) and HDL-cholesterol (HDL-C) were measured (7, 8 and 9 wk) and in vivo lipoprotein metabolism evaluated (after 9 wk). Initially, all monkeys were fed a high-fat, high-cholesterol reference diet [38% of energy (en) from fat, 18%en saturated fatty acids (SFA), 10%en monounsaturated fatty acids (MUFA), 10%en polyunsaturated fatty acids (PUFA), 0.045 mg cholesterol/kJ diet]. Subsequently, monkeys were rotated through two test diets (30%en fat, SFA/MUFA/PUFA 1:1:1, 0.004-0.005 mg cholesterol/kJ diet), in which 80% of the fat was either PF or CF, with the remaining 20% derived from high-linoleic safflower oil. There was no significant difference between the two test diets for TG, TC, nonHDL-C, HDL-C or the ratio of TC/HDL-C. Lipoprotein composition, LDL apolipoprotein B pool size, fractional catabolic rate and transport rate were also not significantly different when monkeys consumed the two test diets. These data suggest that when incorporated into diets following current guidelines and containing adequate PUFA ( approximately 7-9%en), PF and CF similarly affect plasma lipids.
Animals↗
Anticonvulsant effect of nimodipine alone and in combination with diazepam and phenytoin in a mouse model of status epilepticus.
The effect of nimodipine alone and in combination with diazepam or phenytoin was tested in the electroshock-induced mouse model of status epilepticus. Status epilepticus was induced by transauricular electrical stimulation with a stimulus of 15 mA at 0.5, 3, 10, 20 and 30 min, starting half an hour after intraperitoneal administration of vehicle/drug. The median effective doses of diazepam and phenytoin alone and in combination with a fixed dose of nimodipine (24 mg/kg) was calculated. The ED50s of diazepam and phenytoin were found to be 10.5 and 9 mg/kg, respectively. When nimodipine was combined with diazepam or phenytoin, the ED50 values decreased to 3.77 mg/kg and 7.15 mg/kg, respectively. The severity of seizures was also decreased by combination with nimodipine as compared to diazepam and phenytoin given alone. To study the effect of nimodipine on psychomotor impairments produced by diazepam and phenytoin three tests were performed: rotarod, behavioral despair and hole board. Nimodipine did not show protective effects on its own but potentiated the anticonvulsant effects of diazepam and phenytoin. Furthermore, the combination of nimodipine with diazepam and phenytoin produced lesser impairment of psychomotor functions.
Animals↗
Effect of Azadirachta indica (Neem) leaf aqueous extract on paracetamol-induced liver damage in rats.
The effect of aqueous leaf extract of Azadirachta indica (A. indica) was evaluated in paracetamol induced hepatotoxicity in rats. Liver necrosis was produced by administering single dose of paracetamol (2 g/kg, p.o.). The liver damage was evidenced by elevated levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (gamma-GT) and by histopathological observations of liver sections. Aqueous A. indica leaf extract (500 mg/kg, p.o.) significantly (P < 0.01) reduced these elevated levels of AST, ALT and gamma-GT. Paracetamol induced liver necrosis was also found to be reduced as observed macroscopically and histologically.
Acetaminophen↗
A study of hypoglycaemic effects of Azadirachta indica (Neem) in normaland alloxan diabetic rabbits.
Hypoglycaemic effect was observed with Azadirachta indica when given as a leaf extract and seed oil, in normal as well as diabetic rabbits. The effect, however, was more pronounced in diabetic animals in which administration for 4 weeks after alloxan induced diabetes, significantly reduced blood glucose levels. Hypoglycaemic effect was comparable to that of glibenclamide. Pretreatment with A. indica leaf extract or seed oil administration, started 2 weeks prior to alloxan, partially prevented the rise in blood glucose levels as compared to control diabetic animals. The data suggests that A. indica could be of benefit in diabetes mellitus in controlling the blood sugar or may also be helpful in preventing or delaying the onset of the disease.
Animals↗
Differential modulation of nociceptive responses to mu and kappa opioid receptor directed drugs by blood glucose in experimentally induced diabetes rats.
The study has evaluated the effect of diabetes associated hyperglycaemia on nociception and antinociception induced by morphine, buprenorphine and pentazocine in female albino rats. Rats were allocated into 3 groups of 20 each--group I consisted of control having normal blood glucose levels (BGLs), group II consisted of streptozotocin-induced diabetics (STZ-D) having hyperglycaemia and group III consisted of diabetic rats controlled with insulin treatment. Immediately before and 15, 30 min, 1, 2 and 3 hr after injection with test drugs, rats were subjected to a thermal noxious stimulus using tail withdrawal from hot water and tail-flick latencies (TFL) so generated were recorded. Similarly, before and 30, 45 min and 1 hr after injection with drugs rats were subjected to abdominal writhing with hypertonic saline and number of writhes were counted per 90 sec. In STZ-D animals (BGLs 317.95 +/- 3.8 mg/dl) a decreased TFL with an increase in the number of writhes compared to control and diabetes controlled with insulin treatment was observed. Percent maximum possible effect of morphine (5 mg/kg, s.c.) and buprenorphine (2 mg/kg, s.c.) was significantly lower when compared to control as well as STZ-D controlled with insulin treatment groups. Similarly percent protection from writhing of morphine (0.05 mg/kg, s.c.) and buprenorphine (0.01 mg/kg, s.c.) was significantly less in comparison to control and STZ-D controlled with insulin treatment group. However, percent maximum possible effect of pentazocine (20 mg/kg, s.c.) and percent protection from writhing of pentazocine (1 mg/kg, s.c.) was significantly high in STZ-D rats when compared to control and STZ-D rats controlled with insulin treatment groups. The results suggest that both mu and kappa--opioid receptors may be modulated by blood glucose levels possibly involving cellular energetics mediated change in potassium (KATP) channels in females rats, albeit differentially.
Animals↗
Durable remission of locally advanced breast cancer with multimodality management.
We treated 20 women with locally advanced breast cancer between January 1991 and September 1996. The treatment regimen included 4 cycles of intensive doxorubicin (30 mg/m2/d on 3 consecutive days every 2 weeks with G-CSF support), followed by appropriate surgery, followed by high dose therapy with cyclophosphamide, carboplatin and thiotepa (STAMP V, CTCb). Of the 20 patients, seven presented with inflammatory breast cancer, three with Stage IIIB, seven with stage IIIA, one with multifocal Stage IIB and two with Stage IV M1 (ipsilateral supraclavicular lymph node involvement) (including one who had an inflammatory primary) disease. Six patients had not undergone mastectomy at the time of entering the protocol. These six received the doxorubicin in a neoadjuvant fashion and were thus evaluable for tumor response. The remaining 14 received doxorubicin as adjuvant therapy prior to intensification and transplantation. All patients underwent local-regional radiation therapy and were placed on oral tamoxifen. Doxorubicin was well tolerated in this schedule with all but three patients receiving all their cycles on schedule. Both BM and PBPC were easily collected after this regimen and, when reinfused, resulted in the prompt recovery of granulocytes (median 11 days to 500 absolute granulocyte count) and platelets (median 13 days to 20,000 platelets). The six patients who received doxorubicin prior to mastectomy all had major clinical responses, but were found to have microscopic focii of breast cancer in the mastectomy specimens. The overall treatment was well tolerated with the exception of one treatment-related death (5%). The overall and relapse free survival are 70% and 58% respectively with a median follow-up of 40 months (range 12-74 months). When the Stage IV patients are censored, the relapse-free survival rate is 69%. In the bone marrow transplant phase of treatment, the major non-hematologic toxicities were stomatitis (70%) and anorexia requiring parental nutrition (75%).
Adult↗
Myristic acid-rich fat raises plasma LDL by stimulating LDL production without affecting fractional clearance in gerbils fed a cholesterol-free diet.
The imbalance that develops between low-density lipoprotein (LDL) production and clearance during saturated fat consumption is responsible for expanding the circulating LDL pool. To assess the imbalance attributable to fatty acids alone, i.e., without the interaction of dietary cholesterol, the most fat-sensitive species available (the gerbil) was challenged with either a 12:0+14:0 rich-fat (high coconut, low safflower) or high 18:2 (high safflower, low coconut) fat for 4-5 wks. The plasma lipoprotein cholesterol profile, including lipoprotein composition, particle size and 125I-LDL turnover were measured. Although total plasma cholesterol (TC) was threefold higher with saturated fatty acid (SFA) feeding (230 vs. 70 mg/100 mL; 5.9 +/- 0.1 vs. 1.8 +/- 0.05 mmol/L, P < 0. 0001) and LDL cholesterol (LDL-C) was fivefold greater (10 vs. 54 mg/100 mL; 0.26 +/- 0.02 vs. 1.4 +/- 0.02 mmol/L, P < 0.001), the high-density lipoprotein (HDL2) fraction increased the most (27 vs. 79 mg/100 mL; 0.7 +/- 0.02 vs. 2.0 +/- 0.1 mmol/L, P < 0.05) with minimal HDL3 (NS) difference (16 vs. 26 mg/100 mL; 0.43 +/- 0.08 vs. 0. 7 +/- 0.05 mmol/L). Particle composition and size did not differ between groups. LDL kinetic analyses revealed that the fractional catabolic rate did not differ between gerbils with these extreme fat intakes, implicating overproduction and not reduced clearance as the primary consideration in LDL expansion. Thus SFA-induced cholesterolemia can be severe in the absence of dietary cholesterol with a greater impact on high-density lipoprotein than LDL and without an appreciable role attributed to LDL clearance (receptors).
Animals↗
Drug resistant typhoid fever.
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Adolescent↗
Saturated fatty acids and LDL receptor modulation in humans and monkeys.
It has been known for 40 years that dietary saturated fat (SAT FAT) increases plasma cholesterol, including LDL-C and HDL-C. In humans, where LDL-C is typically > 90 mg/dl this SAT FAT effect largely reflects changes in LDL-C pool size. The original human studies suggested that LDL-C expansion during SAT FAT consumption reflected reduced LDL clearance (LDL receptor activity) in hyperlipemics and increased LDL production rates in normolipemics (LDL-C < 100 mg/dl) . This dual explanation is supported by data from several animal models where specific saturated fatty acids (SFAs) have been the focus. However, the situation is complicated by the fact that polyunsaturated fatty acids (PUFAs) oppose SFAs, i.e. PUFAs decrease LDL-C and increase LDL receptor (LDLr) activity, so the effect of SAT FAT intake may represent the combined influence of increased SFAs and decreased PUFAs. In fact, careful scrutiny of primate data suggests a negligible effect of saturated fat on LDL clearance (and receptor activity) in the absence of dietary cholesterol when PUFA intake is adequate (5-10%en) and the lipoprotein profile is relatively normal (LDL-C < 90 mg/dl), i.e. normolipemic situations at the time of dietary intervention. In such cases increases in LDL-C due to SFAs (particularly 12:0+14:0) appear to reflect LDL overproduction associated with a shift in cholesterol from tissues to the plasma cholesteryl ester (CE) pool (both LDL-C and HDL-C) without altering whole-body cholesterol balance. The reason for this shift, which is accompanied by an increase in the plasma oleic/linoleic CE ratio, is unknown but may reflect a decreased rate of CE hydrolysis by the liver. When individuals or animals are rendered hyperlipemic by other factors (e.g. chronic caloric and dietary cholesterol excesses in humans or by cholesterol feeding in animals) specific SFAs (particularly 16:0) can contribute to decreased LDLr activity initiated by a primary factor, such as dietary cholesterol. However, LDLr down-regulation by dietary cholesterol greatly exceeds any contribution from SFAs.
Animals↗
Effects of dietary palmitic and oleic acids on lipoprotein cholesterol.
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Cholesterol, HDL↗