Plasma concentrations and sedative effects of a dexmedetomidine, midazolam, and butorphanol combination after transnasal administration in healthy rabbits.

Plasma concentrations of dexmedetomidine (D = 0.1 mg/kg), midazolam (M = 2 mg/kg), and butorphanol (B = 0.4 mg/kg) were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) after their simultaneous (DMB) transnasal (TN) administration to healthy rabbits. Time-dependent changes in sedation and antinociception were evaluated by measuring a sedation score based on rabbit's posture, loss of the righting, palpebral and pedal withdrawal reflexes and by instrumental monitoring of rectal temperature, heart rate, arterial blood pressure, pulse-oximetry, and capnometry. The peak plasma concentration (Cmax ) of each drug was reached within 5 min (Tmax ) from DMB-TN administration along with deep sedation and analgesia. Such effects subsided after 45 min into a moderate sedation and analgesia lasting for additional 15 min. All rabbits awakened spontaneously and uneventfully 90 min after DMB-TN administration. During the anesthetic procedure, arterial blood pressure markedly decreased and respiratory depression ensued requiring oxygen supplementation. The results of this study show that all three molecules of the DMB combination were absorbed through the TN route, inducing deep sedation and analgesia suitable for minor surgical procedures. Such combination should be used with caution in rabbits bearing cardiovascular or respiratory diseases because of its ability to induce hypotension and respiratory depression.

A PLAC8-containing protein from an endomycorrhizal fungus confers cadmium resistance to yeast cells by interacting with Mlh3p.

Cadmium is a genotoxic pollutant known to target proteins that are involved in DNA repair and in antioxidant defence, altering their functions and ultimately causing mutagenic and carcinogenic effects. We have identified a PLAC8 domain-containing protein, named OmFCR, by a yeast functional screen aimed at identifying genes involved in cadmium resistance in the endomycorrhizal fungus Oidiodendron maius. OmFCR shows a remarkable specificity in mediating cadmium resistance. Both its function and its nuclear localization in yeast strictly depend on the interaction with Mlh3p, a subunit of the mismatch repair (MMR) system. Although proteins belonging to the PLAC8 family are widespread in eukaryotes, they are poorly characterized and their biological role still remains elusive. Our work represents the first report about the potential role of a PLAC8 protein in physically coupling DNA lesion recognition by the MMR system to appropriate effectors that affect cell cycle checkpoint pathways. On the basis of cell survival assays and yeast growth curves, we hypothesize that, upon cadmium exposure, OmFCR might promote a higher rate of cell division as compared to control cells.

Prolactin hyperresponsiveness to D-fenfluramine in drug-free schizophrenic patients: a placebo-controlled study.

BACKGROUND: Functional alterations in the central serotonergic system have been reported in schizophrenia but no conclusive data have been provided. In the present study, we investigated the prolactin (PRL) response to the selective serotonin (5-HT) releasing agent D-fenfluramine in both patients with schizophrenia and matched healthy subjects. METHODS: Sixteen drug-free schizophrenics and 16 healthy subjects were randomized in a double-blind neuroendocrine test to D-fenfluramine (30 mg p.o.) or placebo. Blood PRL and cortisol concentrations were determined by radioimmunoassay, while plasma levels of D-fenfluramine were measured by mass spectrometry. RESULTS: In schizophrenic patients, baseline plasma PRL levels were not different from controls, whereas plasma cortisol concentrations were significantly increased (p < .03). The PRL response to D-fenfluramine was significantly enhanced in patients as compared to matched control subjects (p < .005). Schizophrenics meeting Kane's criteria for previous nonresponse to typical neuroleptics exhibited a PRL response to D-fenfluramine significantly higher than non-drug-resistant patients (p < .04). No significant difference in plasma D-fenfluramine concentrations was observed between schizophrenic and healthy subjects. CONCLUSIONS: These findings suggest a serotonergic hypersensitivity in chronic schizophrenia. This alteration seems to be peculiar to those patients refractory to typical neuroleptics.

Suppression of nocturnal plasma melatonin levels by evening administration of sodium valproate in healthy humans.

To investigate the role of gamma-aminobutyric acid (GABA) in the modulation of human melatonin production, we studied the effects of the acute administration of the GABAergic drug, sodium valproate (VAL), on nocturnal blood melatonin levels in healthy subjects. To this purpose, 4 healthy men and 3 healthy women, aged 24-33 years, underwent three experimental sessions in which they received orally 400 mg VAL, 800 mg VAL, or placebo, in random order, according to a double-blind design. The drug administration was done at 19:00 hours; thereafter, blood samples were collected over the night, in dark conditions with the help of a red light. As compared to placebo, VAL, at the dosage of both 400 and 800 mg, significantly suppressed nocturnal blood melatonin levels, the higher dose being slightly more effective than the lower one. The maximum suppression coincided with the highest plasma levels of valproic acid. These findings support the view that endogenous GABA may participate in the modulation of the activity of the human pineal gland.

Parenteral nutrition support of a patient with chronic mesenteric artery occlusive disease.

Vascular catastrophe resulting in a bowel infarction requiring massive resection is one of the most common indications for long-term total parenteral nutrition (TPN). The causes of mesenteric artery disease include embolic and thrombotic occlusions, nonocclusive mesenteric ischemia, and chronic mesenteric ischemia. This paper describes a case of a patient with chronic ischemia. The indication for TPN was intestinal angina limiting oral intake, not short-bowel syndrome as a result of bowel infarction and surgery. The patient had an extensive history of atherosclerotic disease and abdominal symptoms. Her nutritional status was maintained with TPN and oral intake as symptomatically tolerated. She eventually developed catheter sepsis. Her cardiopulmonary status deteriorated and she died. Progressive mesenteric ischemia and possible infarction may have contributed to her death. The patient had indicated she did not want surgery for a bowel infarction. She did consent to surgical correction of her disease, if feasible. Although TPN can maintain the nutritional and metabolic status of a patient with chronic mesenteric ischemia, the associated risk of catheter sepsis emphasizes the necessity for expedient treatment of the primary pathology.

Valuation of some biological parameters in acute spinal cord trauma: experimental study in rabbits.

The authors investigated the formation of edema consequent to Spinal Cord Injury in rabbits. The goal of this project was to study the accumulation of Water, Sodium, Potassium and Ferrum in traumatized cords in the early time after the acute injury. To this aim a spinal cord trauma was induced in forty unselected animals using the weight-drop method; Water content was measured by wet and dry weight method; Sodium, Potassium and Ferrum content were measured by atomic absorbance spectrophotometry. These parameters were recorded at various time from the cord trauma (30 minutes up to 14 days). The results are presented and discussed with a particular view to the relationships between biological variation and time from the injury.

[Accumulation of heavy metals in biocrystals in the shell of Mytilus galloprovincialis from different zones of the Gulf of Naples]. / Accumulo di metalli pesanti nei biocristalli delle valve di MytI lus g. provenienti da diverse stazioni del golfo di Napoli.

The amounts of Fe, Zn, Cu, Mg were determined in the inner and outer layers of shells of Mytilus g.. Different values significatively between the layers were found only for Mg. The ratio [Me]Calcite/ [Me]Aragonite was calculated and it is not more than one, for all the colonies of different sampling zones. The Authors conclude that perhaps the reason of this behaviour is the different pollution of their habitat.