Acceptability and outcomes of foreskin preservation for phimosis: An Indian perspective.

AIM: Understanding the Indian perspective, effectiveness, and acceptability of prepuce conservation in children with phimosis. Circumcision is performed and recommended far too often for nonphysiological phimosis. Will a less radical approach be acceptable in the subcontinent? METHOD: A two-arm study with the first arm as KAP (knowledge, attitude, and practice) study (n = 502). The second arm recruited deserving boys (n = 47) with symptomatic phimosis (see inclusion criteria). Betamethasone ointment was applied twice daily over the foreskin and gently massaged to stretch the phimotic band. Those who failed were offered lateral preputioplasty or circumcision. Religious beliefs influence attitude and practice and these were looked at with subgroup analysis. RESULTS: Most (85%) knew that circumcision was not the only treatment for phimosis. Though many parents (93%) knew the importance of foreskin cleanliness, few practiced it. The success of the steroid application was 81% (n = 38/47). Eight underwent preputioplasty. Minor discomfort as morbidity was noted. All parents were able to completely retract the foreskin of their children by the end of one month and were happy about the cosmetic result. CONCLUSIONS: KAP data on foreskin health is not available in the subcontinent, and this is a landmark study. Religious belief and community identity play a strong role in decisions related to foreskin preservation. Prepuce hygiene and knowledge about the usefulness of the foreskin is poor. The combination of medical and surgical methods of conserving the prepuce was effective. A high rate of success and the non-mutilating cosmetic result of prepuce preservation were acceptable to these parents.

Assessment of two immunoassays for detection of IgM antibodies to scrub typhus using a serum panel.

Laboratory tests are necessary for diagnosis of scrub typhus (ST) especially in the absence of the distinctive eschar. Performance of an ELISA and ICT (immunochromatography) to detect IgM antibodies to scrub typhus was assessed using a panel of 346 sera chosen from healthy individuals, those with scrub typhus and scrub-typhus like illness. A sensitivity of 98.7% for ST IgM ICT and 97.4% for ST IgM ELISA was observed while specificity was 96.3% for ICT and 95.9% for ELISA. As excellent concordance (98.8%) was noted between the two assays, IgM ICT can be used for rapid diagnosis of scrub typhus. Abbreviations: ST IgM ELISA: Scrub typhus IgM ELISA; ST IgM ICT: Scrub Typhus IgM Immunochromatography, Rapid diagnostic test: RDT.

Masoprocol decreases rat lipolytic activity by decreasing the phosphorylation of HSL.

Masoprocol (nordihydroguaiaretic acid), a lipoxygenase inhibitor isolated from the creosote bush, has been shown to decrease adipose tissue lipolytic activity both in vivo and in vitro. The present study was initiated to test the hypothesis that the decrease in lipolytic activity by masoprocol resulted from modulation of adipose tissue hormone-sensitive lipase (HSL) activity. The results indicate that oral administration of masoprocol to rats with fructose-induced hypertriglyceridemia significantly decreased their serum free fatty acid (FFA; P < 0.05), triglyceride (TG; P < 0.001), and insulin (P < 0.05) concentrations. In addition, isoproterenol-induced lipolytic rate and HSL activity were significantly lower (P < 0.001) in adipocytes isolated from masoprocol compared with vehicle-treated rats and was associated with a decrease in HSL protein. Incubation of masoprocol with adipocytes from chow-fed rats significantly inhibited isoproterenol-induced lipolytic activity and HSL activity, associated with a decrease in the ability of isoproterenol to phosphorylate HSL. Masoprocol had no apparent effect on adipose tissue phosphatidylinositol 3-kinase activity, but okadaic acid, a serine/threonine phosphatase inhibitor, blocked the antilipolytic effect of masoprocol. The results of these in vitro and in vivo experiments suggest that the antilipolytic activity of masoprocol is secondary to its ability to inhibit HSL phosphorylation, possibly by increasing phosphatase activity. As a consequence, masoprocol administration results in lower serum FFA and TG concentrations in hypertriglyceridemic rodents.

Class A scavenger receptor up-regulation in smooth muscle cells by oxidized low density lipoprotein. Enhancement by calcium flux and concurrent cyclooxygenase-2 up-regulation.

Oxidative stress caused by phorbol esters or reactive oxygen up-regulates the class A scavenger receptor (SR-A) in human smooth muscle cells (SMC), which normally do not express this receptor. The increase in SR-A expression correlates with activation of the redox-sensitive transcription factors activating protein-1 c-Jun and CCAAT enhancer-binding protein beta. Here we show that coincubation of SMC with macrophages or oxidized low density lipoproteins (LDL) from macrophage-conditioned medium activates these same regulatory pathways and stimulates SR-A expression. The increased SR-A gene transcription induced by cell-oxidized LDL up-regulated SR-A mRNA and increased by 30-fold the uptake of acetyl LDL, a ligand for the SR-A. Copper-oxidized LDL also increased SR-A receptor expression. Oxidized LDL with a lipid peroxide level of 80-100 nmol/mg of LDL protein and an electrophoretic mobility approximately 1.5 times that of native LDL exhibited the greatest bioactivity. Inhibition of calcium flux suppressed SR-A induction by oxidized LDL. Conversely, calcium ionophore greatly enhanced SR-A up-regulation by oxidized LDL or other treatments that promote intracellular oxidative stress. This enhancement was dependent upon concurrent up-regulation of SMC cyclooxygenase-2 expression and activity and was blocked by the cyclooxygenase-2 inhibitors NS-398 and Resveratrol. In THP-1 cells, oxidized LDL induced monocyte-to-macrophage differentiation and increased SR-A expression. These findings support a role for mildly oxidized LDL in the redox regulation of macrophage differentiation and SR-A expression and suggest that increased vascular oxidative stress may contribute to the formation of both SMC and macrophage foam cells.

Postprandial low-density lipoproteins in type 2 diabetes are oxidized more extensively than fasting diabetes and control samples.

This study examined the kinetics of low-density lipoprotein (LDL) oxidation in the fasting and postprandial states of diabetic and control subjects to determine if LDL oxidation may contribute to accelerated atherosclerosis in diabetes. We compared in vitro oxidation of LDL from 12 control and 13 Type 2 diabetic subjects in the fasting and postprandial states. The extent of oxidation was assessed by length of lag phase, formation of conjugated dienes (CD), lipid peroxides, thiobarbituric acid reactive substances (TBARS), and percentage reduction in free amine groups. Diabetic subjects were significantly older and heavier. Comparisons between control and diabetic subjects in the postprandial state showed that the lag phase was significantly shorter in diabetic subjects than controls (P = 0.005), TBARS were significantly higher (P = 0.006), and levels of CD were higher at 60, 65, and 70 min (P < 0.01). In the fasting state, however, these comparisons were not significant. In diabetic subjects, postprandial samples had a significantly shorter lag phase (P = 0.003), higher TBARS (P = 0.006), and higher levels of CD at 60, 65 (P < 0.001), and 70 min (P = 0.0013) compared to fasting samples. Elevated levels of serum triglycerides in diabetic subjects were negatively correlated to lag phase, in fasting (P = 0.06) and postprandial states (P = 0.002). We conclude that accelerated oxidation of LDL seen in postprandial states in diabetes may be a critical contributor to cardiovascular risks. Elevated levels of serum triglycerides may contribute to the rapid oxidation of LDL seen in diabetic subjects.

Antioxidant supplementation effects on low-density lipoprotein oxidation for individuals with type 2 diabetes mellitus.

OBJECTIVE: This study compared susceptibility to oxidation of low-density lipoproteins (LDL) of non-diabetic and diabetic (Type 2) men and examined the response of diabetic men to antioxidant supplementation (alpha-tocopherol, beta-carotene and ascorbate). RESEARCH DESIGN AND METHODS: Twenty adult non-diabetic and 20 diabetic men were recruited. Oxidation of LDL was assessed by four different assay systems, and the extent of oxidation was assessed by four different measurements. Diabetic men received eight weeks of placebo ("baseline"), twelve weeks of antioxidant supplements ("treated") and eight weeks of placebo ("post-treatment"). Supplements provided 24 mg of beta-carotene, 1000 mg of ascorbate and 800 IU of alpha-tocopherol daily. RESULTS: With Cu oxidation at 37 degrees C, thiobarbituric reactive substances (TBARS) formation was significantly higher (p=0.032) and loss of free amine groups was significantly greater (p=0.013) in the LDL from diabetic subjects than controls. Antioxidant supplementation of diabetic subjects significantly decreased all parameters of LDL oxidation with Cu at 30 degrees C and 37 degrees C. At 30 degrees C the lag phase increased from 55 to 129 minutes (p<0.0001); conjugated diene formation decreased from 1.23 to 0.62 OD units (p<0.0001); TBARS formation decreased from 78 to 33 nmoles MDA/mg LDL protein (p<0.0001); and free amine loss decreased from 41 to 12% (p<0.0001). With Cu oxidation at 37 degrees C, similar changes occurred. CONCLUSIONS: These studies indicate that the LDL from diabetic subjects are more susceptible to oxidation than LDL from non-diabetic subjects. Supplementation of diabetic subjects with antioxidant vitamins significantly decreases susceptibility of LDL to oxidation by Cu. These studies are consistent with epidemiological and intervention studies suggesting that antioxidant vitamin use significantly decreases risk for coronary heart disease.

Decreased protection by HDL from poorly controlled type 2 diabetic subjects against LDL oxidation may Be due to the abnormal composition of HDL.

High plasma triglyceride concentrations in diabetic subjects increase their risk for developing coronary heart disease. Numerous studies have shown that the high density lipoprotein (HDL) composition is abnormal in type 2 diabetic subjects. One study has shown that HDL (lipoprotein A-I) isolated from subjects with non-insulin-dependent diabetes mellitus exhibits a decreased capacity to induce cholesterol efflux. The current study examined the effect of HDL(2) and HDL(3) subfractions from poorly controlled type 2 diabetic and control subjects on THP-1 macrophage-mediated low density lipoprotein (LDL) oxidation. The composition and protective effects of HDL(2), but not of HDL(3), differed significantly between control and diabetic subjects. HDL(2) from diabetics were triglyceride enriched and cholesterol depleted compared with those from controls. Control HDL(2) inhibited LDL oxidation, as assessed by lipid peroxides and electrophoretic mobility, significantly (P<0.05) more than did diabetic HDL(2) in both the fasting and postprandial state. In addition, HDL(2) from diabetics did not protect against apolipoprotein B-100 fragmentation in LDL. Cross-linking in apolipoprotein A-I, oxidized in the presence of LDL, was extensive in HDL(2) from diabetics compared with that from controls. Serum triglyceride concentrations were negatively correlated with protection by HDL(2) (r=-0.673, P<0.05) in diabetic but not in control subjects. HDL(2)-associated platelet-activating factor acetylhydrolase activity was positively correlated with protection by HDL(2) in control (r=0.872, P<0.002) but not in diabetic subjects. In conclusion, compositional alterations in HDL(2) from poorly controlled type 2 diabetic subjects may reduce its antiatherogenic properties.

Masoprocol lowers blood pressure in rats with fructose-induced hypertension.

Rats with fructose-induced hypertension were treated by oral gavage with either masoprocol (nordihydroguaiaretic acid) or vehicle. Masoprocol treatment resulted in significantly (P < .05 to .001) lower values for systolic blood pressure (120 +/- 3 v 164 +/- 5 mm Hg), as well as plasma insulin (30 +/- 5 v 44 +/- 4 microU/mL), free fatty acid (551 +/- 20 v 692 +/- 22 microEq/L), and triglyceride (79 +/- 5 v 219 +/- 32 mg/dL) concentrations. These results indicate that masoprocol, a lipoxygenase inhibitor, is able to lower blood pressure, as well as improve the metabolic abnormalities present in a rodent model of hypertension that simulates the characteristic of many patients with essential hypertension.

Effect of masoprocol on glucose transport and lipolysis by isolated rat adipocytes.

Masoprocol (nordihydroguaiaretic acid) is a lipoxygenase inhibitor isolated from the creosote bush and used by native healers to treat type 2 diabetes. It has been recently shown to decrease serum glucose, free fatty acid (FFA), and triglyceride (TG) concentrations in rodent models of type 2 diabetes. The current study was initiated to quantify the effects of masoprocol incubation of adipocytes isolated from normal rats. The results indicate that masoprocol significantly increased glucose uptake by adipocytes in both the absence and presence of insulin. In addition, the maximal rate of insulin-stimulated glucose transport was increased in adipocytes incubated with masoprocol and the insulin concentration resulting in a half-maximal glucose transport rate (ED50) decreased. Finally, isoproterenol-stimulated increases in FFA and glycerol release were significantly decreased in the presence of masoprocol. These results provide an explanation at the cellular level for the observation that masoprocol decreases serum glucose, insulin, and FFA concentrations in rodent models of type 2 diabetes.