Endomorphin 1 and endomorphin 2 suppress in vitro antibody formation at ultra-low concentrations: anti-peptide antibodies but not opioid antagonists block the activity

Endomorphin 1 (EM-1) and endomorphin 2 (EM-2) were tested for their capacity to alter immune function. Addition of either of these peptides to murine spleen cells in vitro inhibited antibody formation to sheep red blood cells in a bi-phasic dose dependent manner. Maximal inhibition was achieved at doses in the range of 10⁻¹³ to 10⁻¹⁵ M. Neither naloxone (general opioid receptor antagonist) nor CTAP (selective mu opioid receptor antagonist) blocked the immunosuppressive effect. To show that there was specificity to the immunosuppressive activity of the peptides, affinity-purified rabbit antibodies were raised against each of the synthetic EM peptides haptenized to KLH and tested for capacity to inhibit immunosuppression. Antibody responses were monitored by a standard solid phase antibody capture ELISA, and antibodies were purified by immunochromatography using the synthetic peptides coupled to a Sepharose 6B resin. Verification of the specificity of affinity-purified antisera was performed by immunodot-blot and solid-phase RIA assays. The antisera specific for both EM-1 and EM-2 neutralized the immunosuppressive effects of their respective peptides in a dose-related manner. Control normal rabbit IgG had no blocking activity on either EM-1 or EM-2. These studies show that the endomorphins are immunomodulatory at ultra-low concentrations, but the data do not support a mechanism involving the mu-opioid receptor.     

Frequency of abnormal correlation between leptin and the body mass index during first and second generation antipsychotic drug treatment

BACKGROUND: Leptin dysregulation has been implicated in the body weight gain and metabolic dysfunction observed with the second generation antipsychotic drugs (SGAD) olanzapine and clozapine. METHODS: This study quantified the frequency of subjects with abnormal correlation between leptin and the body mass index controlling for gender (defined as being out of the upper or lower 95% confidence interval in the regression line when combining each group with the drug-free subjects) after prolonged treatment with olanzapine (n=126), clozapine (n=62), first generation antiypsychotics (n=91), other SGAD (n=22), other psychotropic drugs (n=65) and drug-free subjects (n=229). RESULTS: None of the analysis was significant (p>0.05). In fact, in 17 out of 20 comparisons, the drug-free group had numerically higher frequencies of outliers than the corresponding treatment group. There were 28 outliers (4.7% of the total sample). In agreement with previous studies, cross-sectional analysis did not report gross alterations in serum leptin levels during olanzapine or clozapine administration. CONCLUSIONS: Longitudinal studies should focus on leptin regulation early on treatment, on the frequency of abnormal leptin receptor sensitivity and/or specific polymorphisms in the leptin allele and on several confounding factors in order to design personalized preventive and therapeutic measures.     

A threshold concentration of FSH is needed during IVM of ex vivo collected human oocytes

Journal of Assisted Reproduction and Genetics - To investigate the effect of different FSH concentrations on human oocyte maturation in vitro and its impact on gene expression of key factors in the...     

Comparison of measurements of time outdoors and light levels as risk factors for myopia in young Singapore children

Aims

To compare methods to measure time outdoor and light levels, two possible predictors of myopia, in Singapore children.

Methods

Outdoor time from a diary and portable light meter over a 1-week period was compared in 117 Singapore children aged 6–12 years with and without myopia. All children wore a (HOBO Pendant temp/light Part # UA-002-64) light meter for 1 week and the parents filled the 7-day outdoor diary to track the outdoor activity.

Results

Mean outdoor time from diary and time with light levels was 5.44 hours per week and 7.91 hours per week, respectively, during school term and school holidays. Time spent with light levels of >1000 Lux from the light meter were 7.08 h per week and 9.81 h per week, respectively, during school term and school holidays. The intraclass correlation coefficients were 0.21 and 0.28 for outdoor time from the diary and light meter (1000 Lux cut-off) during the school term and holidays, respectively. The correlation coefficient was 0.34 (95% CI 0.05, 0.58) for a weekday during school holidays, 0.17 (−0.14, 0.45) for a weekday during school term, 0.07 (−0.16, 0.29) for a weekday during school term, and 0.25 (0.02, 0.46) for a weekend during school term.

Conclusions

The agreement between the light meter and 1-week diary was poor to fair. Both instruments measure different parameters, time outdoors and light intensity, and could therefore capture different aspects of risk in future myopia studies.     

Antagonism of diazepam hyperphagia by propranolol in rats

The effects of adrenergic beta-receptor blockers on the hyperphagia produced by diazepam were studied in free-feeding rats. The hyperphagia produced by 1.0 mg/kg subcutaneous (s.c.) diazepam, was antagonised by dl-propranolol (6.0 mg/kg s.c.) and 1-propranolol (6.0 mg/kg s.c.), but not by d-propranolol (6.0 mg/kg s.c.). Intracerebroventricular administration of dl-propranolol (50, 100, and 200 μg) failed to antagonise this hyperphagia. Other specific β₁ and β₂ blockers, metoprolol (10.0 mg/kg s.c.), and butoxamine (10.0 mg/kg s.c.) also did not antagonise this hyperphagia. It is suggested that some intrinsic property other than β-blockade, tranquilising, or local anesthetic activity is responsible for this antagonism caused by s.c. administration of dl- or l-propranolol.     

A rare congenital anomaly of nose — Accessory nose : Case report

We describe a 21 year old man who was found to have an opening on his external nose since birth. No other clinical and radiological abnormalities were demonstrable elsewhere in his body. The opening is on the lower part of the nose one cm. away from the midline on right side, clinically looking like a sinus. Histological examination of the excised tract showed an organoid structure that was consistent with an“Accessory nose.”     

Single stage management of Gustilo type III A/B tibia fractures: Fixed with nail & covered with fasciocutaneous flap

Purpose: To evaluate the role of immediate and definitive management of Gustilo type III A/B tibia fractures with intramedullary nailing and fasciocutaneous flap. Methods: From August 2010 to July 2012, 22 patients with Gustilo Grade III A/B tibia fractures were managed with a single stage treatment of ipsilateral fasciocutaneous flap & reamed intramedullary nailing and were included in the study. The severity of the injury was calculated with Ganga Hospital injury severity score. Results: The mean age of patients was 41 years and the follow-up time ranged from six months to one year. Among the 22 patients, 73% were type III B fractures with upper leg involved in 55% of them. The time interval from injury to completion of surgery was 8e14 h. The incidence of bone infection requiring secondary procedure was 9%; the major and minor soft tissue complication rate was 9% and 14% respectively. The limb salvage rate was 100%. Conclusion: Multidisciplinary management of severe lower limb trauma is important and provides good outcomes. Intramedullary nailing and immediate flap fixation can achieve early bone union and good soft tissue coverage, leading to good outcomes in patient with Grade III A & B tibia fractures.     

Protective effect of triterpenes on calcium oxalate crystal-induced peroxidative changes in experimental urolithiasis.

Naturally occurring pentacyclic triterpenes of plant origin have been identified as possessing a wide range of pharmacological effects. Lupeol (Lupa-21,20(29) dien, 3beta-ol) has been found to be efficient in reducing the risk of stone formation in animals by way of preventing crystal-induced tissue damage and dilution of urinary stone-forming constituents. In the present study, two structurally related triterpenes, lupeol and betulin (Lupa-20(29)ene-3,28 diol) were assessed for their antilithiatic effect. Foreign body implantation method followed by supplementation of ammonium oxalate was adapted to induce stone formation in the bladder. This led to elevated lipid peroxidation and depleted antioxidant status in the renal tissues. Both the triterpenes were equally efficient in minimizing crystal-induced renal peroxidative changes measured in terms of malondialdehyde and subsequent tissue damage. The antioxidant status, comprising of the enzymatic and non-enzymatic components, was found to be significantly depleted in the kidney and bladder of stone-forming animals. Both lupeol and betulin were comparable in their ability to restore the thiol status and the antioxidant enzymes like superoxide dismutase, catalase and glutathione peroxidase. The mechanism by which the two compounds render protection against oxalate-induced toxic manifestations and free radical production may involve the inhibition of calcium oxalate crystal aggregation and enhancement of the body defence systems. 2000 Academic Press.