Abnormalities of cholesterol metabolism in autism spectrum disorders.

Although Smith-Lemli-Opitz Syndrome (SLOS), a genetic condition of impaired cholesterol biosynthesis, is associated with autism [Tierney et al., 2001; Am J Med Genet 98:191-200.], the incidence of SLOS and other sterol disorders among individuals with autism spectrum disorders (ASD) is unknown. This study investigated (1) the incidence of biochemically diagnosed SLOS in blood samples from a cohort of subjects with ASD from families in which more than one individual had ASD and (2) the type and incidence of other sterol disorders in the same group. Using gas chromatography/mass spectrometry, cholesterol, and its precursor sterols were quantified in 100 samples from subjects with ASD obtained from the Autism Genetic Resource Exchange (AGRE) specimen repository. Although no sample had sterol levels consistent with SLOS, 19 samples had total cholesterol levels lower than 100 mg/dl, which is below the 5th centile for children over age 2 years. These findings suggest that, in addition to SLOS, there may be other disorders of sterol metabolism or homeostasis associated with ASD.     

Effect of gossypol in association with chromium protoporphyrin on heme metabolic enzymes

Gossypol prevents the liberation of oxygen from oxyhemoglobin and exerts a hemolytic effect on erythrocytes. In excessive dosages of gossypol, an extreme burden is placed upon the respiratory and circulatory organs owing to the reduced oxygen carrying capacity of blood. Chromium protoporphyrin (CrPP) has been shown to either competitively suppress or to significantly ameliorate a variety of naturally occurring or experimentally induced forms of jaundice in animals and man. In this communication, a novel tissue dependent response to gossypol (50 micromol/kg bw) and gossypol in association with CrPP (50 micromol/kg bw) is described. Our results revealed that gossypol stimulated the hepatic, splenic, and renal delta-aminolevulinic acid synthase (ALA-S) activity, the heme biosynthetic enzyme, and simultaneous administration of CrPP and gossypol synergized the gossypol-mediated increase of ALA-S activity. Gossypol was found to be a potent stimulator of heme oxygenase (HMOX) activity in rat liver and kidney to varying degrees. This tissue response contrasted with that of the spleen, where gossypol decreased the activity of the enzyme. In consonance with the increased hepatic and renal HMOX activity, a marked increase was observed in total serum bilirubin concentration in gossypol treated rats. When rats were given CrPP simultaneously with gossypol, the gossypol mediated increase in hepatic and renal HMOX activity was effectively blocked. Furthermore, the increase in enzymatic activity was accomplished by a decline in the total microsomal protein content on gossypol administration. These findings emphasize the toxic effect of gossypol in eliciting increased heme degradation by stimulating HMOX activity in the liver and the kidney and the potential usefulness of CrPP in experimental and perhaps clinical conditions in which hyperbilirubinemia occurs.     

Knowledge and perceptions of residents regarding case management of acute diarrhea.

The knowledge and perceptions about case management of acute diarrhea were studied amongst 330 resident doctors working in Pediatric Departments of various Medical Colleges in the country. Our observations highlight the inadequacies in the medical curriculum and deficient clinical training in the management of acute diarrhea in the teaching institutions. Knowledge of signs of dehydration was correctly perceived by only 79.8% interns, 80.9% house physicians and 81.1% postgraduate students. It was appalling to observe that despite spending 1-3 years in pediatric wards, the knowledge and perceptions of postgraduate students had not significantly improved. On the contrary, the responses of postgraduate students were poorer as compared to interns in their perceptions of use of ORT in moderate dehydration (p less than 0.005) and in presence of vomiting (p less than 0.05). Adequate thrust on diarrhea and its management during undergraduate as well as during postgraduate teaching and proper training in diarrhea case management with "hands on training" needs to be viewed as a priority in the teaching institutions.     

Ultrasonographic estimation of fetal gestational age by fetal kidney length

Introduction: Fetal kidney length vs biparietal diameter (BPD) and femur length (FL) were comparatively evaluated and the role of fetal kidney length in estimating gestational age was determined in the second and third trimesters. Materials and methods: The study was carried out on 199 women with singleton uncomplicated pregnancies attending the outdoor patient department (OPD) for routine ultrasound fetal biometry. Fetal kidney length was measured biweekly, between 18 weeks and 38 weeks of gestation. Linear regression models for estimation of gestational age were derived from biometric indices (BPD and FL) and kidney length. Result: The earliest age at which fetal kidney could be seen sonographically was the 18th week of gestation with the mean kidney length of 12 ± 1.31 mm. The mean sonographic kidney length at the 38th week of gestation was 40.4 ± 1.71 mm, indicating that the mean fetal kidney length increases as pregnancy progresses from 18 weeks to 38 weeks of gestation. Conclusion: The best linear regression model for estimating fetal gestational age is femur length, kidney length, and biparietal diameter in that order, with standard error of ±3.85 days, ±8.04 days, and ±8.75 days, respectively.     

The Noscapine Chronicle: A Pharmaco‐Historic Biography of the Opiate Alkaloid Family and its Clinical Applications

Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable “Renaissance drug” worthy of commemoration. Perhaps the only facet of noscapine's profile more astounding than its versatility is its virtual lack of side effects and addictive properties, which distinguishes it from other denizens of Papaver somniferum. This review intimately chronicles the rich intellectual and pharmacological history behind the noscapine family of compounds, the length of whose arms was revealed over decades of patient scholarship and experimentation. We discuss the intriguing story of this family of nontoxic alkaloids, from noscapine's purification from opium at the turn of the 19th century in Paris to the recent torrent of rationally designed analogs with tremendous anticancer potential. In between, noscapine's unique pharmacology; impact on cellular signaling pathways, the mitotic spindle, and centrosome clustering; use as an antimalarial drug and cough suppressant; and exceptional potential as a treatment for polycystic ovarian syndrome, strokes, and diverse malignancies are catalogued. Seminal experiments involving some of its more promising analogs, such as amino‐noscapine, 9‐nitronoscapine, 9‐bromonoscapine, and reduced bromonoscapine, are also detailed. Finally, the bright future of these oftentimes even more exceptional derivatives is described, rounding out a portrait of a truly remarkable family of compounds.     

Autism: The role of cholesterol in treatment

Cholesterol is essential for neuroactive steroid production, growth of myelin membranes, and normal embryonic and fetal development. It also modulates the oxytocin receptor, ligand activity and G-protein coupling of the serotonin-1A receptor. A deficit of cholesterol may perturb these biological mechanisms and thereby contribute to autism spectrum disorders (ASDs), as observed in Smith-Lemli-Opitz syndrome (SLOS) and some subjects with ASDs in the Autism Genetic Resource Exchange (AGRE). A clinical diagnosis of SLOS can be confirmed by laboratory testing with an elevated plasma 7DHC level relative to the cholesterol level and is treatable by dietary cholesterol supplementation. Individuals with SLOS who have such cholesterol treatment display fewer autistic behaviours, infections, and symptoms of irritability and hyperactivity, with improvements in physical growth, sleep and social interactions. Other behaviours shown to improve with cholesterol supplementation include aggressive behaviours, self-injury, temper outbursts and trichotillomania. Cholesterol ought to be considered as a helpful treatment approach while awaiting an improved understanding of cholesterol metabolism and ASD. There is an increasing recognition that this single-gene disorder of abnormal cholesterol synthesis may be a model for understanding genetic causes of autism and the role of cholesterol in ASD.