Diabetes mellitus, arterial hypertension and serum levels of renin

Plasmatic renin levels were measured in 17 adults patients with diagnosis of diabetes mellitus and systemic arterial hypertension. None of them was under antihypertensive therapy. The results obtained showed lessening of renin levels in 13 cases, normal levels in two cases, no valuable results in one and Significative increase in other. Renal biopsy was performed in 8 patients and in all cases nephropathies were demonstrated; only one of them had normal renin levels. We have concluded that more than 75% of our cases were hyporeninemic hypertensive patients. Our findings are according with other medical papers that have been published before. Finally, we try to explain the mechanisms upon which theorethical causes are based.     

The cardiovascular pharmacology of the antibiotic ionophore Ro 2-2985 (X537A)

Ro 2-2985 increased mean arterial blood pressure in both the venous bypass preparation and the intact animal; however, total peripheral resistance increased in the venous bypass preparation with a constant cardiac output but decreased in the intact animal with an increase in cardiac output. These observations indicate a drug-related increase in the distensibility of the aorta at the same arterial pressure. In vivo ventricular function curves were shifted to the left indicating enhanced myocardial performance with the translocation of large volumes of blood to the central circulation since total body venous compliance was significantly decreased. Beta adrenergic blocking doses of propranolol blocked the positive inotropic effect of Ro 2-2985 while myocardial depression produced by toxic doses of propranolol was reversed. This observation suggests several mechanisms for the Ro 2-2985 metabolic mediation of myocardial muscle contraction. The cardiovascular effects produced by Ro 2-2985 were accompanied by a marked polycythemia and a decrease in plasma volume without a change in total circulating blood volume, while blood glucose values showed a nonsignificant increase. Ro 2-2985 produced a marked increase in cardiac output. The increase in myocardial performance appears to be complex since myocardial force of contraction, dT/dt, dP/dt:P40 and Vmax were all increased. RO 2-2985 increased coronary flow without an increase in resistance. There were no significant increases in myocardial arteriovenous glucose, lactate, K+, Ca++, Na+ or Cl.     

Duration of hospitalization for acute bacterial meningitis at Boston City Hospital during 12 selected years, 1935-1972

An analysis is presented of the duration of hospitalization of the patients with acute bacterial (purulent) meningitis which occurred at Boston City Hospital during 12 selected years between 1935 and 1972. Considerable differences in the length of stay in the hospital were noted depending on the bacterial etiology, whether the infection was present on admission or acquired within the hospital, and, of course, whether the patient survived or died. Most of the deaths occurred within the first few days after admission or after the diagnosis was first established, but even among fatal cases, the survival time differed depending on the etiology and site of acquisition of the infection. During the years after effective antibiotics became available the hospital stay of patients who survived after admission for meningococcal, influenzal, or pneumococcal meningitis was shorter than before. The same has not been true for meningitis caused by other gram-positive cocci, gram-negative rods, or mixed infections, probably reflecting the relative ineffectiveness of antimicrobial therapy in such patients.     

Molt induction in lobsters (Homarus americanus) by intramuscular injection of ecdysterone triacetate

The principal component of the successful, molt-inducing ecdysterone acetate mixture was established as ecdysterone triacetate and shown to have the same activity as the acetate mixture. The triacetate induced ecdysis in male lobsters collected in winter and summer and in female lobsters collected in winter. Intramuscular injections of triacetate in ethanol were as effective as those with oil emulsions.     

Exploring the Biocatalytic Scope of Alditol Oxidase from Streptomyces coelicolor

The substrate scope of the flavoprotein alditol oxidase (AldO) from Streptomyces coelicolor A3(2), recombinantly produced in Escherichia coli, was explored. While it has been established that AldO efficiently oxidizes alditols to D ‐aldoses, this study revealed that the enzyme is also active with a broad range of aliphatic and aromatic alcohols. Alcohols containing hydroxy groups at the C‐1 and C‐2 positions like 1,2,4‐butanetriol (K_m=170 mM, k_cat=4.4 s⁻¹), 1,2‐pentanediol (K_m=52 mM, k_cat=0.85 s⁻¹) and 1,2‐hexanediol (K_m=97 mM, k_cat=2.0 s⁻¹) were readily accepted by AldO. Furthermore, the enzyme was highly enantioselective for the oxidation of 1,2‐diols [e.g., for 1‐phenyl‐1,2‐ethanediol the (R)‐enantiomer was preferred with an E‐value of 74]. For several diols the oxidation products were determined by GC‐MS and NMR. Interestingly, for all tested 1,2‐diols the products were found to be the α‐hydroxy acids instead of the expected α‐hydroxy aldehydes. Incubation of (R)‐1‐phenyl‐1,2‐ethanediol with ¹⁸O‐labelled water (H₂¹⁸O) revealed that a second enzymatic oxidation step occurs via the hydrate product intermediate. The relaxed substrate specificity, excellent enantioselectivity, and independence of coenzymes make AldO an attractive enzyme for the preparation of optically pure 1,2‐diols and α‐hydroxy acids.     

Catalytic mechanism and role of hydroxyl residues in the active site of theta class glutathione S-transferases. Investigation of Ser-9 and Tyr-113 in a glutathione S-transferase from the Australian sheep blowfly, Lucilia cuprina

Spectroscopic and kinetic studies have been performed on the Australian sheep blowfly Lucilia cuprina glutathione S-transferase (Lucilia GST; EC 2.5.1.18) to clarify its catalytic mechanism. Steady state kinetics of Lucilia GST are non-Michaelian, but the quite hyperbolic isothermic binding of GSH suggests that a steady state random sequential Bi Bi mechanism is consistent with the anomalous kinetics observed. The rate-limiting step of the reaction is a viscosity-dependent physical event, and stopped-flow experiments indicate that product release is rate-limiting. Spectroscopic and kinetic data demonstrate that Lucilia GST is able to lower the pKa of the bound GSH from 9.0 to about 6.5. Based on crystallographic suggestions, the role of two hydroxyl residues, Ser-9 and Tyr-113, has been investigated. Removal of the hydroxyl group of Ser-9 by site-directed mutagenesis raises the pKa of bound GSH to about 7.6, and a very low turnover number (about 0.5% of that of wild type) is observed. This inactivation may be explained by a strong contribution of the Ser-9 hydroxyl group to the productive binding of GSH and by an involvement in the stabilization of the ionized GSH. This serine residue is highly conserved in the Theta class GSTs, so the present findings may be applicable to all of the family members. Tyr-113 appears not to be essential for the GSH activation. Stopped-flow data indicate that removal of the hydroxyl group of Tyr-113 does not change the rate-limiting step of reaction but causes an increase of the rate constants of both the formation and release of the GSH conjugate. Tyr-113 resides on alpha-helix 4, and its hydroxyl group hydrogen bonds directly to the hydroxyl of Tyr-105. This would reduce the flexibility of a protein region that contributes to the electrophilic substrate binding site; segmental motion of alpha-helix 4 possibly modulates different aspects of the catalytic mechanism of the Lucilia GST.     

A subset of ventral tegmental area neurons is inhibited by dopamine, 5-hydroxytryptamine and opioids

Neurons originating in the ventral tegmental area are thought to play a key role in the formation of addictive behaviors, particularly in response to drugs such as cocaine and opioids. In this study we identified different populations of ventral tegmental area neurons by the pharmacology of their evoked synaptic potentials and their response to dopamine, 5-hydroxytryptamine and opioids. Intracellular recordings were made from ventral tegmental area neurons in horizontal slices of guinea-pig brain and electrical stimulation was used to evoke synaptic potentials. The majority of cells (61.3%) hyperpolarized in response to dopamine, depolarized to 5-hydroxytryptamine, failed to respond to [Met]5enkephalin and exhibited a slow GABAB-mediated inhibitory postsynaptic potential. A smaller proportion of cells (11.3%) hyperpolarized in response to [Met]5enkephalin, depolarized to 5-hydroxytryptamine, failed to respond to dopamine and did not exhibit a slow inhibitory postsynaptic potential. These two groups of cells corresponded to previously described "principal" and "secondary" cells, respectively. A further group of cells (27.4%) was identified that like the principal cells, hyperpolarized to dopamine. However, these "tertiary cells" also hyperpolarized to both 5-hydroxytryptamine and [Met]5enkephalin and exhibited a slow, cocaine-sensitive 5-hydroxytryptamine(1A)-mediated inhibitory postsynaptic potential. When principal and tertiary cells were investigated immunohistochemically, 82% of the principal cells were positive for tyrosine hydroxylase compared with only 29% of the tertiary cells. The 5-hydroxytryptamine innervation of both these cell types was investigated and a similar density of putative contacts was observed near the somata and dendrites in both groups. This latter finding suggests that the existence of a 5-hydroxytryptamine-mediated inhibitory postsynaptic potential in the tertiary cells may be determined by the selective expression of 5-hydroxytryptamine receptors, rather than the distribution or density of the 5-hydroxytryptamine innervation. We conclude that tertiary cells are a distinct subset of ventral tegmental area neurons where cocaine and mu-opioids both mediate inhibition.     

A prospective controlled study of diagnostic imaging for acute shin splints

OBJECTIVE: The purpose of this prospective, observational study was to examine the relationship of clinical examination, plain radiograph (XR), triple-phase bone scan (TPBS), and magnetic resonance imaging (MRI) in the investigation of patients presenting with acute shin splints. METHODS: 23 subjects with exercise induced lower leg pain and diffuse tibial tenderness of less than 3 months' duration were recruited. Subjects were excluded if there was clinical evidence of compartment syndrome, muscle hernia, or stress fracture. Each subject underwent XR, TPBS, and MRI within 2 wk of physical examination. Four asymptomatic controls underwent TPBS and MRI. Clinical findings, XR, TPBS, and MRI findings were independently recorded using a consistent template and subsequently analyzed. A single consensus lesion was chosen that provided the greatest overlap and highest grade to allow comparison of clinical and imaging findings. Sensitivity and specificity were calculated from data relating to clinical findings and diagnostic imaging. RESULTS: Eighteen subjects had bilateral symptoms and five unilateral with a mean duration of symptom of 5.4 wk (+/- 3.5). Of 41 symptomatic lower legs, there were TPBS abnormalities in 36 and MRI findings in 34. Analysis of clinical findings to TPBS and MRI demonstrated a sensitivity and specificity of 84%, 33% and 79%, 33%, respectively. Assuming TPBS as the "gold-standard," MRI findings demonstrated a sensitivity of 95% and specificity of 67%. There was poor agreement between the grading of TPBS and MRI (k = 0.3). In the 5/46 asymptomatic limbs, 3/5 demonstrated uptake on bone scan and 4/5 signal change with MRI. Imaging abnormalities were similarly seen in the four control patients. CONCLUSIONS: MRI may be used rather than TPBS and radiographs for evaluating acute tibial pain in athletes where avoidance of radiation exposure is desirable. Similar sensitivity and specificity may be expected from both investigations; however, in the light of abnormal TPBS and MRI findings in control and asymptomatic limbs, we recommend further studies be performed to define the extent of nonpathological TPBS and MRI changes.