Histamine is an intracellular messenger mediating platelet aggregation.

Inhibition of human platelet aggregation by N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE), a novel antagonist of histamine binding, suggested that histamine might serve a critical role in cell function. Phorbol-12-myristate-13-acetate (PMA) or collagen was found to increase platelet histamine content in parallel with promotion of aggregation. Inhibitors of histidine decarboxylase (HDC) suppressed both aggregation and the elevation of histamine content, whereas DPPE inhibited aggregation only. In saponin-permeabilized platelets, added histamine reversed the inhibition by DPPE or HDC inhibitors on aggregation induced by PMA or collagen. The results indicate a role for histamine as an intracellular messenger, which in platelets promotes aggregation.

A novel role for vitamin K1 in a tyrosine phosphorylation cascade during chick embryogenesis.

The development of the embryo is dependent upon a highly coordinated repertoire of cell division, differentiation, and migration. Protein-tyrosine phosphorylation plays a pivotal role in the regulation of these processes. Vitamin K-dependent gamma-carboxylated proteins have been identified as ligands for a unique family (Tyro 3 and 7) of receptor tyrosine kinases (RTKs) with transforming ability. The involvement of vitamin K metabolism and function in two well characterized birth defects, warfarin embryopathy and vitamin K epoxide reductase deficiency, suggests that developmental signals from K-dependent pathways may be required for normal embryogenesis. Using a chick embryogenesis model, we now demonstrate the existence of a vitamin K1-dependent protein-tyrosine phosphorylation cascade involving c-Eyk, a member of the Tyro 12 family, and key intracellular proteins, including focal adhesion kinase (pp125FAK), paxillin, and pp60src. This cascade is sensitive to alteration in levels or metabolism of vitamin K1. These findings provide a major clue as to why, in the mammalian (and human) fetus, the K-dependent proteins are maintained in an undercarboxylated state, even to the point of placing the newborn at hemorrhagic risk. The precise regulation of vitamin K1-dependent regulatory pathways would appear to be critical for orderly embryogenesis.

Biochemical and ultrastructural studies suggest that the effects of thapsigargin on human platelets are mediated by changes in intracellular calcium but not by intracellular histamine.

The involvement of intracellular histamine in thapsigargin (Tg)-induced platelet aggregation was studied. Platelet aggregation induced by 0.25 and 0.5 microM Tg was not accompanied by a rise in intracellular histamine but a significant (p < 0.01) increase in the level of intracellular histamine was observed at 1 microM Tg. Preincubation of platelets with inhibitors of histamine metabolizing enzymes had little effect on intracellular histamine levels in platelets stimulated by 0.5 microM Tg. In addition, the inhibitors of histidine decarboxylase (HDC), alpha-methyl histidine (alpha-MH) and alpha-fluoromethyl histidine (alpha-FMH) failed to inhibit Tg-induced aggregation. The intracellular histamine receptor antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine. HCl (DPPE), inhibited Tg-induced aggregation but with IC50 values dependent on the concentration of agonist used. The inhibitory effects of DPPE on Tg-induced aggregation were not reversed by the addition of histamine to saponin-permeabilized platelets suggesting non-histamine mediated effects of DPPE on Tg-induced aggregation. Tg stimulated an increase in the cytosolic free calcium concentration which was unaffected by DPPE indicating that the effects of DPPE are also not due to the inhibition of mobilization of cytosolic calcium. The ultrastructural studies suggest that the major Tg-induced changes (pseudopod formation and granule centralization) are consistent with a primary role for Tg to mobilize calcium; DPPE had very little effect on these ultrastructural changes. The results indicate that the effects of Tg on human platelets are mediated by an increase in cytosolic calcium but not by intracellular histamine.

The riddle of vitamin K1 deficit in the newborn.

Vitamin K in the fetus and newborn is maintained at levels less than that necessary to achieve full gamma-carboxylation of the K-dependent proteins, including those required for hemostasis. As the infant matures and even into adulthood, there is no significant storage pool for this vitamin, and a K1-deficient state can be produced by placing an adult on a K-deficient diet for 7 to 10 days. Questions arise as to why the level of vitamin K is so rigidly controlled and why the placental gradient in humans and other mammals maintains the fetus in a K-"deficient" state. The evidence is reviewed that suggests that K-dependent proteins are ligands for receptor tyrosine kinases, which, in the rapidly proliferating cell milieu of the fetus, control growth regulation. Increased stimuli may result in growth dysregulation whereas conversely, the further depletion of vitamin K-dependent proteins, as in warfarin toxicity, depletes the required stimuli for normal embryogenesis. These findings argue for the need for tightly controlled levels of vitamin K consistent with normal embryogenesis.

Circadian periodicity of urinary volume, creatinine and 5-hydroxyindole acetic acid excretion in healthy Indians.

The circadian periodicity of urinary output, creatinine (Cr) and 5-hydroxyindole acetic acid (5-HIAA) excretion was studied under near-tropical conditions in 130 healthy volunteers (65 men and 65 women, 16-75 years of age) with a diurnal activity from about 06:30 to about 22:00 and nocturnal rest. These volunteers were divided into 4 groups, 16-30, 31-45, 46-60 and 61-75 years of age, comprising 20, 20, 15 and 10 participants of each gender, respectively. A marked circadian rhythm was recorded for urine volume, Cr and 5-HIAA excretion in healthy Indians of different ages. The acrophase tended to be delayed in the older age group. The relative amplitude decreased with advancing age, notably in women. Overall, men produced a larger urine volume as compared to women. Excretions of Cr and 5-HIAA in healthy Indian volunteers of different ages may be influenced by diet, societal relations, climate and/or geographic location. The contribution of such factors in metabolism and degradation warrants further study.

Trigeminal and peripheral neuropathy in a patient with systemic sclerosis and silicosis.

The unusual occurrence of cranial (trigeminal) and peripheral neuropathy in a case of progressive systemic sclerosis (PSS) is described. The possible association of PSS with silicosis is also discussed.

Histamine as an intracellular messenger in human platelets.

The results of investigations in platelets provide evidence for an intracellular messenger role for histamine. Studies of neutrophils and of cellular proliferation suggest that there may be a wider role for histamine as an intracellular messenger modulating activation processes in cells.

Histo-functional status of kidney in leprosy.

A study of 64 cases of leprosy (44 lepromatous and 20 nonlepromatous) revealed that the duration of the disease has a significant relationship with renal involvement (chi 2 = 16.9, P less than 0.001). Proteineuria, microscopic haematuria, granular and hyaline casts are mainly seen in lepromatous cases and specially with lepra reaction (100%) while few of the non-lepromatous (2%) cases may show these abnormalities. Impaired renal functions are mostly observed in lepromatous leprosy (62.9%) specially those with lepra reaction (100%) while 2% nonlepromatous cases have these impaired renal functions. Histo-pathological studies revealed non-specific changes in 44.4% of cases and those of chronic pyelonephritis in 15.5% of the cases. Renal amyloidosis is less common occurrence (4.4%). The specific lesion, that is 'leproma kidney', is rare and seen in one patient only. Acid fast bacilli could not be seen in any of the kidney tissue. It is therefore, concluded that the renal involvement in the form of inflammatory lesions and non-specific changes in the glomeruli and tubules are very common in lepromatous leprosy specially during the reactive phase.

Some pharmacological actions of the essential oil of Blumea membranacea.

The essential oil obtained from the plant Blumea membranacea produced a marked and long lasting fall in blood pressure in anaesthetized dogs. The oil exerted a direct depressant action on frog heart and spasmolytic effect on rabbit ileum. It also depressed the conditioned avoidance response, adversely affected rotarod performance and potentiated the pentobarbitone induced hypnosis in rats.

Fructose 1, 6 bisphosphatase activities in mouse liver as a function of age.

Neutral fructose 1, 6 bisphosphatase activity increases till 7 days, after which, a decline is observed postnatally upto 30 days. Alkaline fructose 1, 6 bisphosphatase follows the same pattern. The optimum activity of fructose 1, 6 bisphosphatase in mouse liver at pH 6.5 and 9.0 of all the periods, suggests the presence of both neutral and alkaline enzyme during the developmental period studied. On the basis of similarity observed in optimum pH, the same properties of enzyme at all the developmental stages studied, could not be ruled out.

Significance of serum immunoglobulin levels in conglomeration with trans-sternal phlebography in the phlebography management of breast cancer.

The study was conducted on 63 patients with breast lump and twenty normal healthy females. In benign breast disease, a significant (P < 0.001) rise in serum IgA, significant (P < 0.001) decrease in IgG and no change in IgM levels was seen before operation. A significant decrease (P < 0.001) in serum IgA and significant increase in IgG and IgM was observed post operatively. In carcinoma breast, a significant (P < 0.001) elevation in IgA, IgG and IgM levels was found pre-operatively with a concomitant decrease in serum IgA and IgG and increase in serum IgM levels, post operatively. Trans-sternal phlebography (TSP) carried out with 95.23% success has revealed significant (P < 0.001) change in the staging of carcinoma breast. The increased levels of serum immunoglobulins associated with the patients of carcinoma breast with metastasis has led to conclude that these levels, if punctuated with TSP findings can lead to better assessment of the staging of carcinoma breast and thereby its management.

Incidence of Hypothyroidism in Infertile Patients with Menstrual Irregularities

Background: - It is important to estimate in females the level of serum thyroid hormones throughout infertility to avoid its existence later on. The aim in this study, was to estimate thyroid function tests in infertile patients with menstrual irregularities. Methodology: - This case control study was performed in 90 infertile patients with menstrual irregularities and 50 healthy matched women. Biochemical parameters were measured was serum hormones triiodothyronine (T3), tetraiodothyronine (T4) and serum thyroid stimulating hormone (TSH). Result: - Serum T3, T4 and TSH level were statistically significant in infertile women. Serum thyroid stimulating hormone level was found at higher side in infertile women. Conclusion: - This study concludes that, high occurrence of hypothyroidism was found in infertile women and it shows a positive correlation with menstrual disorder.