Oncogenicity testing of 2-ethylhexanol in Fischer 344 rats and B6C3F1 mice

An increasing number of studies, both experimental and epidemiologic, have provided evidence that filtering glaucoma surgery may be less effective than initially described. Of a number of risk factors for failure, duration and number of antiglaucoma drugs prior to surgery seem to play a critical role and highly accumulated antiglaucoma topical treatments significantly reduce success rates. Histopathological studies have confirmed that topically applied drugs may exert toxic effects to the corneoconjunctival surface, and induce chronic infraclinical inflammation, as shown by the presence of immune and inflammatory infiltrates in multitreated eyes. The origin of topical inflammation has not yet been clearly determined, but a common component of ophthalmic drugs, the benzalkonium chloride used as preservative in almost all antiglaucoma preparations, has shown strong evidence of toxicity. A number of questions remain to be investigated, but suppression of preservatives from chronically applied drugs should be a critical issue in the near future.     

Skeletal alkaline phosphatase activity is primarily released from human osteoblasts in an insoluble form, and the net release is inhibited by calcium and skeletal growth factors

Low-affinity penicillin-binding proteins (PBPs), which participate in the beta-lactam resistance of several pathogenic bacteria, have different origins. Natural transformation and recombination events with DNA acquired from neighbouring intrinsically resistant organisms are responsible for the appearance of mosaic genes encoding two or three low-affinity PBPs in highly resistant strains of transformable microorganisms such as Neisseria and Streptococcus pneumoniae. Methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococcal strains possess the mecA determinant gene, which probably evolved within the Staphylococcus genus from a closely related and physiologically functional gene that was modified by point mutations. The expression of mecA is either inducible or constitutive. A stable high-level resistant phenotype requires the synthesis of a normally constituted peptidoglycan. Enterococci have a natural low susceptibility to beta-lactams related to the presence of an intrinsic low-affinity PBP. Highly resistant enterococcal strains overexpress this PBP and/or reduce its affinity.     

The Pseudomonas syringae pv. tomato HrpW protein has domains similar to harpins and pectate lyases and can elicit the plant hypersensitive response and bind to pectate

The host-specific plant pathogen Pseudomonas syringae elicits the hypersensitive response (HR) in nonhost plants and secretes the HrpZ harpin in culture via the Hrp (type III) secretion system. Previous genetic evidence suggested the existence of another harpin gene in the P. syringae genome. hrpW was found in a region adjacent to the hrp cluster in P. syringae pv. tomato DC3000. hrpW encodes a 42. 9-kDa protein with domains resembling harpins and pectate lyases (Pels), respectively. HrpW has key properties of harpins. It is heat stable and glycine rich, lacks cysteine, is secreted by the Hrp system, and is able to elicit the HR when infiltrated into tobacco leaf tissue. The harpin domain (amino acids 1 to 186) has six glycine-rich repeats of a repeated sequence found in HrpZ, and a purified HrpW harpin domain fragment possessed HR elicitor activity. In contrast, the HrpW Pel domain (amino acids 187 to 425) is similar to Pels from Nectria haematococca, Erwinia carotovora, Erwinia chrysanthemi, and Bacillus subtilis, and a purified Pel domain fragment did not elicit the HR. Neither this fragment nor the full-length HrpW showed Pel activity in A230 assays under a variety of reaction conditions, but the Pel fragment bound to calcium pectate, a major constituent of the plant cell wall. The DNA sequence of the P. syringae pv. syringae B728a hrpW was also determined. The Pel domains of the two predicted HrpW proteins were 85% identical, whereas the harpin domains were only 53% identical. Sequences hybridizing at high stringency with the P. syringae pv. tomato hrpW were found in other P. syringae pathovars, Pseudomonas viridiflava, Ralstonia (Pseudomonas) solanacearum, and Xanthomonas campestris. DeltahrpZ::nptII or hrpW::OmegaSpr P. syringae pv. tomato mutants were little reduced in HR elicitation activity in tobacco, whereas this activity was significantly reduced in a hrpZ hrpW double mutant. These features of hrpW and its product suggest that P. syringae produces multiple harpins and that the target of these proteins is in the plant cell wall.     

Renal responses of Australian lungfish to vasotocin, angiotensin II, and NaCl infusion

The Australian lungfish (Neoceratodus forsteri) responds to intravenous injections of 0.63 ng/kg or more of arginine vasotocin with increased dorsal aortic blood pressure, inulin clearance, urine flow, and tubular rejection of Na+. Single injections of 1 ng/kg or more of angiotensin II or norepinephrine also increase dorsal aortic pressure but do not cause consistent diuresis and natriuresis, Continuous infusions of angiotensin II or repeated injections of norepinephrine produce sustained hypertension and more modest diuresis and natriuresis than are seen after injections of arginine vasotocin that cause less hypertension. Infusions of isosmolar or hyposmolar NaCl solutions increase blood pressure, inulin clearance, urine flow, and tubular Na+ rejection in a manner resembling the response to argininge vasotocoin injections. These data are consistent with the hypothesis that arginine vasotocin is released in response to volume expansion in lungfishes and that it may act on the kidney as a diuretic and natriuretic hormone. They do not rule out a more direct action of expansion on renal functions.     

Segmental renin sampling and partial nephrectomy in renal hypertension

Selective renin sampling from renal vein tributaries identified a high-renin source in the lower pole of the left kidney in a 16-year-old boy who had gradually developed hypertension after blunt left renal trauma. Localized renin secretion from the ischemic pole was associated with suppression of renin secretion from both the contralateral kidney and the normal part of the affected kidney. Removal of ischemic tissue by partial nephrectomy produced sustained correction of hypertension. The findings indicate that segmental renin sampling can define indications for partial nephrectomy in renal hypertension.     

Swelling Control in Uranium Carbide

Fine particles were dispersed in a fuel structure to trap fission gases as very small bubbles and thereby reduce fuel swelling. The dispersions were made by adding 1.5 to 3.0 wt% W to the UC; the specimens were irradiated to a maximum of ∼2 at.% burnup. Density changes were used as the measure of swelling; there was much scatter in the results. Tungsten reduced the swelling when it was uniformly dispersed. For some samples having excess U and W or a segregated structure, W increased the swelling. The results tentatively confirm that fine particles are of value in reducing fission-gas swelling of carbide fuels.     

Effect of dehydration on stimulation of ADH release by heterologous renin infusions in conscious dogs

The effect of acute administration of morphine on cerebral excitability was investigated in rats with two convulsant drugs: flurothyl (hexafluorodiethyl ether) and pentylenetetrazol (PTZ). In the flurothyl study, adult male Sprague-Dawley (S-D) rats were injected subcutaneously with morphine sulfate in doses ranging from 0.5 to 256 mg/kg. At 15, 30, 60 and 120 minutes after morphine injection, flurothyl was administered by inhalation and the seizure thresholds were determined. In the PTZ study, 64 mg/kg of morphine sulfate were injected subcutaneously into both S-D and CFN (Wistar-derived) rats. Thresholds to PTZ seizures were measured after administering the convulsant either by the intraperitoneal or intravenous route. The data revealed an anticonvulsant action of morphine on both flurothyl and PTZ. Peak time for this effect on flurothyl seizures was 30 minutes after subcutaneous administration of the opiate, with the maximal anticonvulsant activity appearing at the 64-mg/kg dose. The increase in seizure threshold in S-D rats at this dose was 36% with flurothyl, 94% with intravenous PTZ and 352% with i.p. PTZ. Morphine had a less dramatic influence on raising the latter seizure threshold in the CFN than in the S-D strain. The graded dose-related anticonvulsant action is independent of the respiratory depression associated with morphine administration and appears to be a reflection of an altered central nervous system excitability produced by the narcotic in rats.