Glibenclamide Therapy in Diabetes Mellitus

In an initial trial of glibenclamide in the treatment of maturity onset diabetes mellitus 28 patients were treated for up to one year and no toxic effects or side-effects were encountered. The hypoglycaemic potency of this drug is such that 5 mg. of glibenclamide corresponds to about 1,500 mg. of tolbutamide and 375 mg. of chlorpropamide.     

Haemodynamic Studies with Peruvoside in Human Congestive Heart Failure

The immediate haemodynamic effects of peruvoside, a cardiac glycoside obtained from the Indian plant Thevetia neriifolia Juss, were studied in six patients with congestive heart failure. The drug was found to have an immediate and powerful positive inotropic and negative chronotropic effect, like ouabain, on the failing human heart. Oral peruvoside was also effective in the treatment of congestive heart failure when used on a short-term as well as a long-term basis. It therefore seems that peruvoside is a useful cardiac glycoside in the management of congestive heart failure in man as a quick-acting intravenous preparation. It is equally effective when used orally.     

Mining of genomic databases to identify novel biodesulfurizing microorganisms

The commercialization of the biocatalytic desulfurization process does not seem to be realistic in the near future because of the low desulfurization rate of the known microorganisms. Hence, the future development will depend on either genetically modifying the currently available bacteria or identifying novel biodesulfurizers. In this study an in silico method to identify new biodesulfurizing microorganisms was adopted. By screening the available genomic databases, 13 novel desulfurizing microorganisms belonging to 12 genera were identified. Several of these could be of immense utility as they have both environment pollutant and industrial waste degrading capability.     

RAPD analysis of induced mutants of groundnut (Arachis hypogaea L.)

Radiation-induced mutants of groundnut cv. Spanish Improved showing distinct morphological differences and the parent were screened for RAPD variability. The analysis revealed characteristic band differences among the 12 mutants and the parent. The polymorphic RAPD bands were dominant in the F₁ and segregated in a Mendelian fashion in the F₂. The RAPD technique brought out greater genome variability than RFLP.     

Cold tolerance in CCl4-treated rats and its modification by administration of garlic oil and glucose

Male Wistar rats weighing 150–200 g maintained under standard laboratory conditions and given Hindustan Lever Pellets and waterad libitum were exposed to –20°C for determination of the rate of fall of rectal temperature and survival time. The rate of fall of body temperature was significantly increased and the survival time was reduced, when animals were given an intraperitoneal injection of 1 ml/kg BW of CCl₄ 24 h but not 2 h earlier. Pre-treatment of the animals with 0.006 ml of garlic oil in a 2% solution of arachis oil for 3 days gave a significant protection to the animals against the CCl₄-induced fall in cold tolerance. Administration of glucose orally 300 mg in 2 ml of saline eliminated the CCl₄-induced fall in cold tolerance. The animals displayed a hypoglycemia 24 h, but not 2 h after injection of CCl₄. CCl₄-induced hypoglycemia was reduced by pre-treatment with garlic oil. The results indicate that the CCl₄-induced reduction in cold tolerance is secondary to hypoglycemia and not due to the direct effect of CCl₄ on the thermoregulatory mechanism in the CNS. The critical level of blood glucose below which the cold tolerance is reduced was found to be 76 mg/100 ml of blood.     

Effects of thyroxine and triiodothyroacetic acid on cerebral myelin lipids

Neonatal rats, thyroidectomized at one day of age, received either no replacement therapy or daily subcutaneous injections of 100 μg/kg body weight of thyroxine (T₄) or equal molar amounts of triiodothyroacetic acid (T₃AC) from day 6 to day 26. Myelin lipid was isolated from the rat cerebrums and the cholesterol, cerebroside and total phospholipid content were determined. Cerebral myelin lipid weights were decreased in the neonatally thyroidectomized and T₄ treated rats. The myelin lipid weights of the T₃AC treated rats were not different from those treated with T₄. The lipid composition remained unchanged in the T₃AC, T₄, and thyroidectomized groups when compared with the normal rats. These results indicate that T₃AC and T₄ administration have similar effects on CNS myelination in brains of neonatally thyroidectomized rats.     

Gluconeogenesis from L-serine in rat liver.

Livers of fed and fasted rats were perfused $\text{in situ}$ in the presence and absence of 4.8 mM quinolinate, an $\text{in vivo}$ inhibitor of phosphoenolpyruvate carboxykinase. An assay of the hepatic activities of serine dehydratase and serine pyruvate transaminase and a comparison of the $\text{in vivo}$ incorporation of radioactivity from serine 3-¹⁴C and serine U-¹⁴C into blood glucose were also carried out in the above nutritional states. Our results demonstrate that gluconeogenesis from L-serine proceeds through two pathways. One, involving the reversal of the biosynthetic route of serine, bypasses conversion to pyruvate phosphoenolpyruvate and oxaloacetate and is not inhibited by quinolinate. This pathway appears to be the only one active in the fed state but produces a very insignificant amount of glucose. The other involves serine dehydratase mediated conversion of serine to pyruvate, is inhibited by quinolinate and becomes predominant during starvation.     

Extracellular Heat Shock Protein 90 Signals through Subdomain II and the NPVY Motif of LRP-1 Receptor to Akt1 and Akt2: a Circuit Essential for Promoting Skin Cell Migration In Vitro and Wound Healing In Vivo

Normal cells secrete heat shock protein 90 alpha (Hsp90α) in response to tissue injury. Tumor cells have managed to constitutively secrete Hsp90α during invasion and metastasis. The sole function of extracellular Hsp90α (eHsp90α) is to promote cell motility, a critical event for both wound healing and tumor progression. The mechanism of promotility action by eHsp90α, however, has remained elusive. A key issue is whether eHsp90α still acts as a chaperone outside the cells or is a new and bona fide signaling molecule. Here, we have provided evidence that eHsp90α utilizes a unique transmembrane signaling mechanism to promote cell motility and wound healing. First, subdomain II in the extracellular part of low-density lipoprotein receptor-related protein 1 (LRP-1) receives the eHsp90α signal. Then, the NPVY but not the NPTY motif in the cytoplasmic tail of LRP-1 connects eHsp90α signaling to serine 473 but not threonine 308 phosphorylation in Akt kinases. Individual knockdown of Akt1, Akt2, or Akt3 revealed the importance of Akt1 and Akt2 in eHsp90α-induced cell motility. Akt gene rescue experiments suggest that Akt1 and Akt2 work in concert, rather than independently, to mediate eHsp90α promotility signaling. Finally, Akt1 and Akt2 knockout mice showed impaired wound healing that cannot be corrected by topical application with the eHsp90α protein.