X-ray and neutron diffraction studies of crystallinity in hydroxyapatite coatings

To standardize industrial implant production and make comparisons between different experimental results, we have to be able to quantify the crystallinity of hydroxyapatite. Methods of measuring crystallinity ratio were developed for various HA samples before and after plasma spraying. The first series of methods uses X-ray diffraction. The advantage of these methods is that X-ray diffraction equipment is used widely in science and industry. In the second series, a neutron diffraction method is developed and the results recorded are similar to those obtained by the modified X-ray diffraction methods. The advantage of neutron diffraction is the ability to obtain measurements deep inside a component. It is a nondestructive method, owing to the very low absorption of neutrons in most materials.     

Issues in contemporary fluid management

Fluid management strategies need to be guided by an understanding of the pathophysiologic mechanisms underlying fluid imbalance. In the hypovolaemic patient, reduced circulating blood volume and venous return and, in severe cases, altered tissue perfusion may initiate a cascade of pathophysiologic processes culminating in multiple organ failure. The objectives of fluid management are to maintain adequate blood pressure, tissue oxygenation and intravascular fluid volume. Both crystalloids and colloids can be useful for these purposes. In the hypovolaemic patient with normal pulmonary function, the use of colloids to maintain colloid osmotic pressure can limit the development of peripheral as well as pulmonary oedema. However, choice of fluid is less important in states of increased lung capillary permeability. Further evidence is needed to broaden understanding of the optimal roles for particular fluid management strategies. Experimental models can make an important contribution in gathering such evidence. Rigorous pharmacoeconomic studies are also needed to define the benefits and costs of differing fluid regimens.     

Tumour necrosis factor in neonatal listeriosis: a case report

A newborn with fatal neonatal listeriosis developed septic shock, neutropenia, thrombocytopenia and profound hypoxaemia due to severe pulmonary hypertension. Tumour necrosis factor , interleukin-1- and interferon- serum concentrations were markedly elevated, suggesting the participation of these cytokines in the aetiopathogenesis of shock induced by Listeria monocytogenes in the neonate.Abbreviations IFN- interferon- - IFN- interferon- - IL-1 interleukin-1 - MPA monocytosis producing agent - TNF- tumour necrosis factor      

In Vivo Reversal of Multidrug Resistance by Two New Dihydropyridine Derivatives, S16317 and S16324

Two new dihydropyridine derivatives with low calcium channel affinity, S16317 and S16324, were found to fully overcome multidrug resistance in vitro. These two compounds increased doxorubicin cytotoxicity on the human COLO 320DM cell line and completely reversed the vincristine resistance of murine P388/VCR cells. In vivo, S16324 administered p.o. (200 mg/kg on days 1 to 4) or i.p. (50mg/kg on days 1, 5, 9) in combination with vincristine (i.p.) restored the antitumor activity of vincristine in P388/VCR-bearing mice. S16317 showed a reversing activity when administered p.o., i.v. (days 1 to 4) or i.p. (days 1, 5, 9) at the same dose (25 mg/kg), suggesting a remarkable bioavailability. Moreover, these two compounds potentiated the antitumor activity of vincristine in the sensitive P388 leukemia, increasing the number of long-term survivors. These results suggest that combination chemotherapy using S16317 or S16324 would be effective not only in circumventing multidrug resistance but also in preventing the emergency of a population of resistant tumor cells in sensitive tumors.     

Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes.

Clinical or biochemical findings were reevaluated in 34 pediatric patients with primary renal tubular hypokalemic metabolic alkalosis. The patients were subdivided into two groups. Bartter syndrome (primary renal tubular hypokalemic metabolic alkalosis with normocalciuria or hypercalciuria) was diagnosed in 18 patients with molar urinary calcium/creatinine ratios greater than 0.20, and Gitelman syndrome (primary renal tubular hypokalemic metabolic alkalosis with magnesium deficiency and hypocalciuria) was diagnosed in 16 patients with molar urinary calcium/creatinine ratios less than or equal to 0.20 and plasma magnesium levels less than 0.75 mmol/L. Some clinically important differences between the groups were observed. Patients with Bartter syndrome were often born after pregnancies complicated by polyhydramnios (8/18) or premature delivery (7/18) and had short stature (11/18) or polyuria, polydipsia, and a tendency to dehydration (16/18) during infancy (12/18) or before school age (18/18). Patients with Gitelman syndrome had tetanic episodes (12/16) or short stature (3/16) at school age (14/16). We conclude that the Bartter and Gitelman syndromes represent two distinct variants of primary renal tubular hypokalemic metabolic alkalosis and are easily distinguished on the basis of urinary calcium levels.     

Thyrotropin-releasing hormone regulates the diurnal variation of pyroglutamyl aminopeptidase II activity in the male rat adenohypophysis

OBJECTIVE: Thyrotropin-releasing hormone (TRH) is inactivated in the extracellular compartment by pyroglutamyl aminopeptidase II (PPII), a narrow specificity ectopeptidase present in the brain and in the lactotrophs of the adenohypophysis. TRH and various hypothalamic/paracrine agents regulate the activity of PPII on the surface of adenohypophyseal cells in primary culture. The activity of the hypothalamic-pituitary-thyroid axis presents circadian variations including an increase of serum thyrotropin levels in the early hours of the day. The purpose of this study was to determine whether adenohypophyseal PPII activity fluctuates during the daytime in the male rat and the role of TRH in these regulatory events in vivo. RESULTS: Adenohypophyseal PPII specific activity and mRNA levels presented diurnal variations. A decrease in specific activity occurred with a minimum between 0930 and 1130 h, associated with increased serum thyrotropin levels. PPII mRNA levels were lowest at 0800 h. Intraperitoneal injection at 0800 or 1000 h of [3-Me-His(2)]-TRH, a potent agonist of the TRH receptor, reduced PPII specific activity at 30 min post-injection which was followed by a return to basal levels at 2 h. A second phase of decrease occurred between 4 and 8 h post-injection. Intravenous injection of a TRH-immune serum induced, at 2 h post-injection, an increase in adenohypophyseal PPII specific activity, which lasted up to 6 h. CONCLUSIONS: Adenohypophyseal PPII activity and mRNA levels fluctuate during the day; TRH down-regulates PPII activity in vivo, contributing to some of these variations. These new findings, and previous data, suggest that adenohypophyseal PPII activity varies in distinct physiological events, in response to endocrine and hypothalamic/paracrine factors, potentially modulating responses to TRH.     

Hypothyroidism related to excess iodine

WOLFF-CHAIKOFF'S EFFECT: The thyroid gland has a capacity to reduce thyroid hormone production in the presence of excess iodine by reducing the organification of the iodine. This Wolff-Chaikoff effect is observed after 48 hours and protects the organism from excessive synthesis of the thyroid hormones. This effect is usually temporary and within a few days thyroid hormone synthesis returns to normal through the so-called 'escape' phenomenon. However in a few normal individuals and in some susceptible patients, the escape does not occur. THE CONTEXT OF OCCURRENCE: Iodine-induced hypothyroidism is observed in fetuses, newborn, adults and in the elderly. It is observed in individuals without underlying overt thyroid disorder, and specially in patients with autoimmune thyroiditis or those previously treated for thyroid diseases (Graves' disease, subacute or pospartum thyroiditis, iatrogenic thyroid dysfunction...). FROM A CLINICAL AND PROGRESSIVE POINT OF VIEW: The hormone deficiency is of obvious clinical expression, or sometimes discreet and revealed by hormone exploration. It is usually temporary, regressing with a few days or weeks after iodine withdrawal. Nevertheless, some patients require transient hormone replacement therapy.     

Oxytocin-induced renin secretion by denervated kidney in anaesthetized rat

The effects of oxytocin on renin secretion by denervated kidney were investigated in vivo, by infusing the peptide directly into the renal artery of anaesthetized rats. Renin secretion was calculated by the renal veno-arterial difference in plasma renin activity multiplied by renal plasma flow. The intra-renal arterial (i.r.a.) infusion of oxytocin (1.5 or 15 ng/kg/min, 10 min) induced a sixfold increase in renin secretion as compared to vehicle-treated controls, without effects on renal blood flow, mean arterial blood pressure, glomerular filtration rate or natriuresis. The effect of oxytocin (1.5 ng/kg/min) was prevented by pretreatment with an oxytocin receptor antagonist, desGly-NH(2),d(CH(2))(5)[D-Tyr(2),Thr(4),Orn(8)]vasotocin] (5.6 microg/kg bolus i.v. 20 min before oxytocin infusion, followed by 2.8 microg/kg/min i.r.a.). Nadolol (2.5 mg/kg i.v.), a beta-adrenoceptor antagonist, also blocked the oxytocin-induced increase in renin secretion. These results show that oxytocin is able to stimulate renin release by activating oxytocin receptors but that beta-adrenoceptors also seem to be involved.     

Enhancement of fotemustine (Muphoran) cytotoxicity by amifostine in malignant melanoma cell lines

Fotemustine (Muphoran, S10036), a nitrosourea derivative active in the treatment of malignant melanoma and primary brain tumors, was evaluated in combination with the free radicals cytoprotective agent amifostine (Ethyol, WR-2721) and its alkaline phosphatase (AP)-generated active metabolite WR-1065 in four human melanoma (RPMI-7950, SK-MEL2, SK-MEL5 and WM-115) and lung fibroblast (MRC-5) cell lines. No difference in AP activity was found among the melanoma cell lines, but AP was found to be significantly higher in MRC-5. For combination experiments, cell lines were first exposed to amifostine or WR-1065 for 15 min and then exposed to fotemustine for two cell doubling times. Non-cytotoxic amifostine and WR-1065 concentrations used (0.2 and 0.6 and 0.1 and 0.3 mmol/l, respectively) were deduced from clinically achieved plasma values. Interactions were analyzed from the variations in IC(50) of fotemustine induced by pre-exposure of the cells to amifostine or WR-1065. In all melanoma cell lines, amifostine enhanced the cytotoxic activity of fotemustine as a significant decrease in IC(50) was observed. No significant difference was found between synergistic effects achieved with amifostine and WR-1065 given at half concentrations. No differential effect was found in the MRC-5 cell line as compared with the melanoma cell lines. Expression variation of O(6)-methylguanine methyltransferase was not found to be implicated in the interaction. The present results demonstrating that amifostine or its main active metabolite do not impair the cytotoxicity of fotemustine justify an extensive clinical evaluation of this combination in metastatic melanoma.