Plasmodium yoelii YM MAEBL protein is coexpressed and colocalizes with rhoptry proteins

Several human diseases, in particular metabolic disorders, often lead to the accumulation of characteristic metabolites in plasma, urine and cells. The selected diseases of this type include cystinuria and homocystinuria. In the typical laboratory diagnosis of these two diseases, a positive nitroprusside test is followed by quantitative analysis of urine cysteine and homocysteine in order to differentiate between cystinuria and homocystinuria. A sensitive and reproducible assay for total urine cysteine and homocysteine has been developed. The essential steps in the assay include conversion of disulphides to free thiols with tributylphosphine, conjugation of the thiols with 2-chloro-1-methyl pyridinium iodide, separation of S-pyridinium derivatives of cysteine and homocysteine from other endogenous urine thiol derivatives by reversed-phase high-performance liquid chromatography, and detection and quantitation by spectrophotometry. The method has a sensitivity of 4 pmol and is reproducible, intra- and inter-day coefficients of variation are from 1.37 to 4.14% and from 2.38 to 5.01%, respectively. The mean concentration of total urine cysteine and homocysteine in healthy donors (7 men and 7 women) were for women. 92.0 +/- 45.8 and 16.4 +/- 4.8 respectively, and for men 120.9 +/- 46.6 and 21.5 +/- 7.4 nmol/ml, respectively. Total urine homocysteine represents approximately 17.7% of cysteine in the urine of normal individuals.     

Diagnostic laparoscopy in 1043 patients with suspected acute appendicitis

OBJECTIVE: To evaluate the efficacy of diagnostic laparoscopy in patients with suspected acute appendicitis, the number of complications associated with the laparoscopic technique, and the effect of leaving a macroscopically normal-looking appendix in place. DESIGN: Three prospective protocols. SETTING: Three departments of surgery, one in Norway and two in Sweden. SUBJECTS: 1043 patients aged 15 years or over. INTERVENTIONS: Diagnostic laparoscopy in patients with signs and symptoms of acute appendicitis who were to be operated on. MAIN OUTCOME MEASURES: Morbidity, mortality, and histological appearance of removed appendices, and outcome whether or not the patient was operated on. RESULTS: 819 patients had appendectomies (61% laparoscopically and 39% by conversion to open operation) with a total complication rate of 10%. In 211 patients a diagnostic laparoscopy was done as a single procedure. There were 181 women in this group and 86 of them had gynaecological disorders. The complication rate was 2% among these 211 patients and after a follow up of two years no patients had been readmitted for appendicectomy. 13 patients were subjected to other open procedures. The overall mortality was 0.4%. CONCLUSION: Diagnostic laparoscopy is safe and can be recommended in patients with suspected acute appendicitis, particularly in women. A macroscopically normal-looking appendix can be left in place.     

Pharmacological aspects of mouse hind-paw oedema induced by Lachesis muta rhombeata venom

Pharmacological aspects of mouse hind-paw oedema induced by subplantar injections of Lachesis muta rhombeata (LMR) venom were investigated. The oedema induced by subplantar injections of 10 to 50 ng/g of LMR venom is dose dependent, with onset, peak and duration at 30, 60 and 180 min, respectively. Subplantar injection of 30 ng/g of Bothrops jararaca (BJ) venom induced oedema that has the same intensity as 30 ng/g of LMR venom but lasts for more than 4 h suggesting different time course. Systemic effects or haemorrhage were not observed with doses less than 50 ng/g. Oedema is not due to the presence of oedematogenic amines since dialysis did not change the oedema induced by 30 ng/g of LMR venom. Part of the oedema induced by LMR venom is due to a thermolabile fraction since pre-heating the venom at 100 degrees C for 15 min induced a significant reduction (56.19 +/- 6.8%) of the oedematogenic activity. The oedema induced by LMR venom is possibly induced by release of a pharmacological active substance at the site of injection. Histamine, arachidonate metabolites, nitric oxide and serotonin may play important roles in the oedematogenic effect of LMR venom since pre-treatment of mice with pyrilamine, indomethacin, dexamethasone, L-NAME and methysergide induced a significant reduction (49.86 +/- 10%; 51.06 +/- 5.9%; 77.66 +/- 3.6%; 73.30 +/- 6.1% and 93.77 +/- 2.8%, respectively) of the oedema formation. The present results demonstrate that the oedema induced by LMR and BJ venoms may be triggered and maintained by different pharmacological mechanisms. Since methysergide and L-NAME were the most active inhibitors of the oedema we can suggest that a link between serotonin release by the venom and a NO synthase activation may be an important step in the oedema formation induced by LMR venom.     

The human type 1 inositol 1,4,5-trisphosphate receptor from T lymphocytes. Structure, localization, and tyrosine phosphorylation

Inositol 1,4,5-trisphosphate receptors (IP3R) are intracellular calcium release channels involved in diverse signaling pathways. An IP3R is thought to play a role in mobilizing calcium required for activation of T lymphocytes. The IP3R is a tetrameric structure comprised of four approximately 300-kDa subunits encoded by a approximately 10-kilobase mRNA. In the present study we determined the structure of the human type 1 IP3R expressed in T lymphocytes (Jurkats). The IP3R in human T cells had a predicted molecular mass of 308 kDa and was most similar to the non-neuronal form of the rodent type 1 IP3R. Two putative tyrosine phosphorylation sites were identified, one near the amino terminus and one near the putative channel pore at the carboxyl terminus. During T cell activation the IP3R was tyrosine phosphorylated. A site-specific anti-IP3R antibody was used to localize the carboxyl terminus of the IP3R to the cytoplasm in T cells.     

Alfentanil slightly increases the sweating threshold and markedly reduces the vasoconstriction and shivering thresholds

BACKGROUND: Hypothermia is common in surgical patients and victims of major trauma; it also results from environmental exposure and drug abuse. In most cases, hypothermia results largely from drug-induced inhibition of normal thermoregulatory control. Although opioids are given to a variety of patients, the thermoregulatory effects of opioids in humans remain unknown. Accordingly, the hypothesis that opioid administration impairs thermoregulatory control was tested. METHODS: Eight volunteers were studied, each on 3 days: (1) a target total plasma alfentanil concentration of 100 ng/ml, (2) control (no drug), and (3) a target alfentanil concentration of 300 ng/ml. Each day, skin and core temperatures were increased sufficiently to provoke sweating. Temperatures subsequently were reduced to elicit peripheral vasoconstriction and shivering. Mathematical compensations were made for changes in skin temperature using the established linear cutaneous contributions to control of sweating (10%) and to vasoconstriction and shivering (20%). From the calculated thresholds (core temperatures triggering responses at a designated skin temperature of 34 degrees C) and unbound plasma alfentanil concentrations, the individual concentration-response relationship was determined. The concentration-response relationship for all the volunteers was determined similarly using total alfentanil concentrations. RESULTS: In terms of unbound concentration, alfentanil increased the sweating threshold (slope = 0.021 +/- 0.016 degrees C.ng-1.ml; r2 = 0.92 +/- 0.06). Alfentanil also significantly decreased the vasoconstriction (slope = -0.075 +/- 0.067 degrees C.ng-1.ml; r2 = 0.92 +/- 0.07) and shivering thresholds (slope = -0.063 +/- -0.037 degrees C.ng-1.ml; r2 = 0.98 +/- 0.04). In terms of total alfentanil concentration (degrees C.ng-1.ml), the sweating threshold increased according to the equation: threshold (degrees C) = 0.0014[alfentanil] + 37.2 (r2 = 0.33). In contrast, alfentanil produced a linear decrease in the core temperature, triggering vasoconstriction: threshold (degrees C) = -0.0049[alfentanil] + 36.7 (r2 = 0.64). Similarly, alfentanil linearly decreased the shivering threshold: threshold (degrees C) = -0.0057[alfentanil] + 35.9 (r2 = 0.70). CONCLUSIONS: The observed pattern of thermoregulatory impairment is similar to that produced by most general anesthetics: a slight increase in the sweating threshold and a substantial, linear decrease in the vasoconstriction and shivering thresholds.     

The two nonallelic Xenopus insulin genes are expressed coordinately in the adult pancreas

Eighty-eight [corrected] patients selected from a depot neuroleptic clinic in the hospital outpatients department were assessed clinically on various demographic and clinical variables with a view to determining the factors that may contribute to high rates of rehospitalisation amongst schizophrenics in remission. It was found that rehospitalisation rates during the preceding 5 years correlated with an early age of onset of illness, severity of positive and affective symptoms, current neuroleptic dose and total AIMS score, all reflecting the severity of underlying psychotic disorder and the neuroleptic treatment required to treat the psychosis. Poor compliance with neuroleptic prophylaxis was not found to be of importance in contributing to high relapse rates in this sample. It was concluded that patients who repeatedly relapse may do so because of the clinical characteristics of their illness.     

Kinetic study of controlled release of VPA and DPH antiepileptic drugs using biocompatible nanostructured sol–gel TiO<Subscript>2</Subscript>

Sol–gel TiO₂ porous matrix was used to host valproic acid (VPA) and phenytoin (DPH), which are commonly used as antiepileptic drugs. The addition of these drugs was carried out during the synthesis in the hydrolysis stage. In vitro short term kinetic studies on drug liberation showed that almost all samples followed a first order kinetics with the exception of one sample which had a linear behavior. High resolution electron microscopy revealed the existence of nanocrystalinity in all samples, however, electron diffraction patterns showed that some were predominantly amorphous while in others suggested a greater density of nanocrystals. NMR studies demonstrated that VPA was less mobile in a more crystalline TiO₂ matrix than when the TiO₂ is mainly amorphous. Some features of the kinetics of drug liberation are explained in terms of the competition between nanocrystallinity and drug content. The reservoirs were implanted by means of stereotactic surgery in Wistar rats in which epilepsy was previously induced following the Kindling model of epilepsy. The efficiency of the reservoirs was follow by electroencephalography (EEGs). In vivo studies revealed that a more crystalline sample was more effective in preventing further epileptic events than samples with a higher content of VPA but predominantly amorphous.     

A metabolic syndrome in whites and African-Americans. The Atherosclerosis Risk in Communities baseline study

The efficacy of microspheres made of polylactic acid polyglycolic acid copolymer mixed with blood clot as a delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2) was evaluated and the long term behaviour of rhBMP-2 in rats was studied. Twenty micro grams of rhBMP-2 in 200 microliter carrier (blood coagulum and polylactic acid polyglycolic acid porous microspheres) were implanted subcutaneously over both sides of the chest muscles in 40 5-week-old male Long Evans rats. The control group were implanted with carrier alone. Specimens were retrieved after 3 days and weekly for 9 weeks. Outcome was measured by signs of bone formation on low power radiographs, and signs of bony growth on histological examination. There were no signs of foreign body or inflammatory reactions to the carrier in either group. In the experimental group signs of bone formation had started to appear by the end of the first week, and there was a gradual increase in both radio-opacity and size during the observation period. Histologically the bony growth was beginning to mature by 4 weeks and was fully mature by 7-9 weeks. In contrast there was no sign of cartilage or bone formation in the control group and the carrier had resorbed by 4-6 weeks. It is concluded that rhBMP-2 implanted in a carrier consisting of blood clot and porous microspheres made of polylactic acid polyglycolic acid induces rapid proliferation of mesenchymal cells that lead to formation of cartilage and bone by 7 days which had matured by 9 weeks. rhBMP-2 in this carrier may be useful clinically because of its capacity to induce early formation of bone.     

Citation for the 1998 Gerald D. Aurbach Lecture Award of the Endocrine Society to Dr. JoAnne S. Richards

Rectal stenosis following low anterior resection is common. Several methods of treatment have been described. We introduce a simple method for the treatment of anastomotic stenosis using a conventional proctoscope and an electric knife with a Foley catheter as an anvil. Under direct vision, this technique can afford accurate and safe incision of stenosis.