Systematic review and meta-analysis of clinical trials examining the effect of hyperbaric oxygen therapy in people with diabetes-related lower limb ulcers.

AIM: To examine the efficacy of hyperbaric oxygen therapy in healing diabetes-related lower limb ulcers through a meta-analysis of randomized clinical trials. METHODS: A literature search was conducted to identify appropriate clinical trials. Inclusion required randomized study design and reporting of the proportion of diabetes-related lower limb ulcers that healed. A meta-analysis was performed to examine the effect of hyperbaric oxygen therapy on ulcer healing. The secondary outcomes were minor and major amputations. RESULTS: Nine randomized trials involving 585 participants were included. People allocated to hyperbaric oxygen therapy were more likely to have complete ulcer healing (relative risk 1.95, 95% CI 1.51-2.52; P<0.001), and less likely to require major (relative risk 0.54, 95% CI 0.36-0.81; P=0.003) or minor (relative risk 0.68, 95% CI 0.48-0.98; P=0.040) amputations than control groups. Sensitivity analyses suggested the findings were dependent on the inclusion of one trial. Adverse events included ear barotrauma and a seizure. Many of the trials were noted to have methodological weaknesses including absence of blinding of outcome assessors, lack of a justifiable sample size calculation and limited follow-up. CONCLUSIONS: This meta-analysis suggests hyperbaric oxygen therapy improves the healing of diabetes-related lower limb ulcers and reduces the requirement for amputation. Confidence in these results is limited by significant design weaknesses of previous trials and inconsistent findings. A more rigorous assessment of the efficacy of hyperbaric the efficacy of hyperbaric oxygen therapy is needed.

Role of multivitamins, micronutrients and probiotics supplementation in management of HIV infected children.

OBJECTIVES: To assess the immuno-clinical response of micronutrients supplementation in human immunodeficiency virus (HIV) infected children (both on and without antiretroviral therapy) and to assess the role of probiotics in improvement of CD4 counts in HIV infected children not on antiretroviral therapy. METHODS: This was an open labeled randomized control study, conducted in Department of Pediatrics and Antiretrovial Therapy (ART) Center, S.N. Medical College, Agra. One hundred and twenty seven HIV infected children aged ≤ 15 y were included in the study. Enrolled children were randomized to receive micronutrients for 6 mo or probiotics for 3 mo. Children who did not receive supplements served as control. Change in WHO clinical stage, immunological stage, CD4 counts and body mass index (BMI) status were taken at the end of 6 mo. In probiotic group, mean CD4 count were taken as outcome measure. A detailed history, examination and WHO clinical staging were recorded for all the patients. RESULTS: In micronutrient supplemented group (not on ART), significant improvement was seen in WHO clinical staging (p = 0.049) when compared to controls after 6 mo. Probiotic supplemented group showed significant increase in CD4 counts compared to control group (p = 0.0022) in children >5 y. Control group showed significant decline in CD4 count in children ≤5 y (-65.3 cells/mm(3), p=0.005) and in children >5 y (-87.9 cells/mm(3), p=0.05) after 12 wk of supplementation. CONCLUSIONS: Probiotics supplementation has shown significant improvement in CD4 counts. Micronutrients supplementation has shown significant delay in the progression towards advance stage of disease.

The mistletoe lectin I--phloretamide structure reveals a new function of plant lectins.

The X-ray structure at 2.7A resolution of the complex between the European mistletoe lectin I (Viscum album, ML-I) and the plant growth hormone, 3-(p-hydroxyphenyl)-propionic acid amide (phloretamide, PA) from xylem sap has revealed the binding of PA at the so far undescribed hydrophobic cavity located between the two subunits of this ribosome-inhibiting protein. No such cavity is observed in related lectins. The binding of PA is achieved through interactions with the non-conserved residues Val228A, Leu230A, Arg388B, and the C-terminal Pro510B. It is conceivable that binding of PA to ML-I is part of a defence mechanism of the parasite against the host, whereby the parasite prevents the growth hormone of the host from interfering with its own regulatory system. The specific binding of PA to ML-I indicates that heterodimeric RIPs are multifunctional proteins whose functions in the cell have not yet been fully recognized and analyzed.

Stone fragility: its therapeutic implications in shock wave lithotripsy of upper urinary tract stones.

OBJECTIVE: To analyse the impact of stone composition on stone fragility (fragmentation) and clearance of upper urinary tract stones after shock wave lithotripsy (SWL). MATERIAL AND METHODS: Between 1st July 1998 and 31st July 2001, 300 renal and ureteric units of 290 patients (10 being bilateral) underwent SWL for upper urinary tract calculi. The degree of fragmentation was divided into four types: (I) Excellent, (II) Good, (III) Fair and (IV) No fragmentation. Stone composition was done by X-ray diffraction crystallography. A statistical comparison was made between degree of fragmentation, number of shock waves delivered, voltage setting, number of sessions required and requirements of adjuvant procedures according to the stone composition. RESULTS: Stone analysis revealed that 90% of the patients had calcium oxalate stones. Of these 80% were calcium oxalate monohydrate (COM) and 20% calcium oxalate dehydrate (COD). Struvite, apatite and uric acid stones comprised of 6%, 3% and 1% respectively. Type-I fragmentation was achieved up to 63.96%, 50% and 100% in COD, struvite and uric stones respectively as compared to 44.9% and 44.44% for COM and apatite stones. Type-III fragmentation was seen up to 8.79% and 33.3% respectively in COM and apatite as compared to 5.55% or less in other types of the stones suggesting that COM and apatite stones produce larger fragments. The mean number of shock waves, voltage and number of treatments was significantly higher for COM and apatite stones (p value < 0.005) with a stone free rate of only 65-66% and 65-68% respectively at three months (p value < 0.001). Similarly the number of adjuvant procedures required in COM alone was more, i.e. 31 as compared to 17 procedures in rest of the other kinds of stones (p value < 0.05). CONCLUSION: Stone composition in Indian subcontinent is different from the western world. Fragility of a stone varies with the composition of the stone and affects the therapeutic results.

Purification, crystallization, and X-ray diffraction studies of lactotransferrin from buffalo colostrum.

Lactotransferrin is an iron-binding protein. It has been purified from buffalo colostrum. The purified lactotransferrin has been crystallized in 10% ethanol solution. The crystals are orthorhombic and the space group is P2(1)2(1)2(1) with unit cell dimensions a = 161.70 A, b = 155.75 A, c = 113.48 A. The asymmetric unit contains three molecules of the protein with a solvent content of about 59%. The crystals were stable in the X-ray beam and diffract beyond 3.5 A resolution. The native data have been collected and the structure determination is in progress.

Regulation of prolactin secretion by hypothalamus in some cold blooded vertebrates.

Effect of homoplastic hypothalamic extract (HHE) on the release of prolactin from the pituitary gland of three aquatic animals -- the fish, Clarias batrachus, the amphibian, Rana tigrina and the reptile, Natrix piscator was studied. Release of prolactin from the pituitary gland in the above animals was blocked within 4 hours by CG 603 (100 microgram/g body wt.) injection. Administration of HHE and perphenazine (15 microgram/g body wt.) in such animals resulted in significantly increased level of prolactin in the blood serum within one hour of treatment indicating an accelerated release of prolactin from the pituitary gland. Injection of cerebral cortical extract failed to induce such response in any of the specimens. From the findings of the present experimentation it is evident that the hypothalamus in C. batrachus, R. tigrina and N. piscator contained predominantly prolactin-release stimulatory factor (PRF) at the time of assessment. Probably in the aquatic poikilotherms where prolactin is not essential for their survival in hypophysectomized condition, hypothalamus contains PRF at least for some period in a year.

Short-term effect of two pesticides on the survival, ovarian 32P uptake and gonadotrophic potency in a freshwater catfish, Heteropneustes fossilis (Blouch).

The effects of pesticides containing either an organophosphate malathion (Cythion) or an organochloride endrin (Hexadrin) on the survival, ovarian 32P uptake and the gonadotrophic potency of the pituitary gland and serum of Heteropneustes fossilis were studied for 96 h. Hexadrin was found to be more toxic than Cythion. Reduced ovarian 32P uptake and a significantly decreased level of total gonadotrophin in the pituitary gland and serum were seen when fish were placed either in a drug concentration that had been found to kill half the fish in 96 h or in a safe concentration of Hexadrin and cythion in aquarium water. Administration of LH or homologous pituitary extract during the exposure of the fish to the pesticides increased the ovarian 32P uptake. The data suggest that these pesticides retarded gonadotrophin secretion which in turn reduced ovarian 32P uptake. However, they did not interfere with the effects of exogenous LH or pituitary extract at the dose levels tested.

Ovarian activity, and total gonadotrophin and gonadotrophin releasing hormone levels in response to some synthetic non-steroidal ovulating agents in the catfish, Heteropneustes fossilis (Bloch).

Effects of clomiphene citrate, cyclofenil and prostaglandins (PGE1 and PGF2 alpha) on ovarian 32P uptake, on gonadotrophin levels in the pituitary gland and blood serum and on a gonadotrophin releasing hormone-like (GnRH-like) substance in the hypothalamus were investigated in Heteropneustes fossilis. These drugs were very effective in increasing the serum level of gonadotrophin with a subsequent increase in ovarian 32P uptake in sham-hypophysectomized recipients. All the drugs except cyclofenil failed to stimulate 32P incorporation by the ovary in hypophysectomized fish. Clomiphene citrate and cyclofenil also induced a significant increase in the GnRH-like factor in the hypothalamus of H. fossilis. Such a response was not obtained in fish treated with PGE1 and PGF2 alpha. It seems likely that the action of clomiphene is routed through the hypothalamo-pituitary-ovarian axis and that of prostaglandins directly through the pituitary-ovarian axis. The action of cyclofenil is bimodal; one effect like that of clomiphene and the other direct upon the ovary probably by increasing its sensitivity to the available gonadotrophin.

Effect of methallibure on gonadotrophic content, ovarian 32P uptake and gonadosomatic index in the freshwater catfish, Heteropneustes fossilis (Bloch).

Gonadotrophin content in the pituitary gland and blood serum as well as ovarian 32P uptake were studied in response to methallibure treatment in H. fossilis. There was a marked reduction in the gonadotrophic activity of the pituitary gland and blood serum within 3 weeks of methallibure treatment (100 microng/g). A simultaneous significant reduction was also recorded in the ovarian activity of these fish. The fall in ovarian activity caused by methallibure could not be prevented by the administration of LH, FSH or LH+FSH. After cessation of methallibure treatment, LH+FSH (50 microng each) administration restored ovarian activity. It is evident from these results that methallibure alters the secretion of gonadotrophin, and also prevents its action on the ovary.

Hypothalamic stimulation of prolactin release in a freshwater catfish, Heteropneustes fossilis.

Hypothalamic extract has been found to contain certain factor(s) which triggers the release of prolactin from the pituitary gland. In assay recipients, hypothalamic extract injection was as effective as perphenazine-HCl treatment in triggering the release of prolactin from pituitary gland. Rise in prolactin concentration of serum and resultant decrease in pituitary prolactin level in response to hypothalamic extract administration suggests that hypothalamus in H. fossilis has prolactin releasing factor(s). This releasing effect of hypothalamus seems to be specific since cortical extract injections were ineffective in producing the similar response.