Effects of central monoamine compounds on tranylcypromine-induced barbital-withdrawal convulsions

Challenge with tranylcypromine (Tcp) during barbital (B) withdrawal induces doserelated clonic-tonic convulsion (C-TC), which is also related to the severity of withdrawal signs and their changes with the passage of time. The effects of neuropharmacological agents on the Tcp-induced convulsions were observed. dl-Propranolol, phentolamine, phenoxybenzamine and methysergide had been administered intraperitoneally 20≈30 minutes before Tcp challenge. B-withdrawn rats had been pretreated with α-methyl-p-tyrosine, 5-hydroxytryptophan, p-chlorophenylalanine or reserpine, or with the combination of iproniazid and reserpine (5 hrs after iproniazid administration) before Tcp challenge. α-MT and dl-propranolol inhibited B withdrawal convulsion markedly, though high doses of dl-propranolol rather tended to show a less inhibitory effect on the convulsion. α-Adrenoceptor blockers scarely inhibited the convulsion. Methysergide or 5-HTP failed to inhibit, but PCPA intensified the convulsion. Reserpine, when administered alone, aggravated the convulsion, but when administered after iproniazid, inhibited it significantly. These findings suggested that the balance between the activities of noradrenergic and serotonergic neurons might be of importance in the manifestation of B withdrawal convulsions, the former probably being excitatory and the latter, inhibitory.     

Comparison of vasodilator potency of adrenomedulling and proadrenomedullin N-terminal 20 peptide in human

Adrenomedullin (ADM) and proadrenomedullin N-terminal peptide (PAMP), both of which are derived from preproadrenomedullin, are reported to have a potent hypotensive effect in animals. However, no data are available concerning the vasodilatory potency of PAMP or comparing this potency to that of ADM in human vasculature. We examined the effects of intra-arterial infusion of graded doses of ADM (1.25, 2.5, 5.0 and 7.5 pmol/min per 100 ml of tissue) and PAMP (125, 250, 500, 750 and 1000 pmol/min per 100 ml of tissue) on total forearm blood flow and forearm skin blood flow in 11 healthy subjects. ADM increased total forearm blood flow from 2.9 +/- 0.4 to 8.6 +/- 1.1 ml/min per 100 ml (p < 0.01), and skin blood flow from 0.07 +/- 0.02 to 0.14 +/- 0.03 volts (p < 0.01). In contrast to this potent vasodilatory effect, a significant rise in forearm skeletal blood flow was seen only in response to the maximum dose of PAMP (from 2.7 +/- 0.5 to 5.3 +/- 1.0 ml/min per 100 ml; p < 0.01). In addition, PAMP had no significant vasoactive effect on skin blood flow (from 0.06 +/- 0.02 to 0.09 +/- 0.03 volts; NS). In conclusion, the skeletal muscle vasodilator potency of PAMP is less than one hundredth of that of ADM in human forearm. Given its weak dilator potency, it seems unlikely that PAMP alone could significantly regulate resistance vessel tone as a circulating hormone in humans.     

Efficacy of the pain pump catheter in immediate autologous breast reconstruction

The purpose of the investigation was to evaluate the efficacy of a slow bupivacaine infusion at postoperative surgical sites in immediate breast reconstruction patients. This prospective study included 16 patients who underwent autologous breast reconstruction with a latissimus dorsi pedicled flap immediately after mastectomy. A two-site infusion kit with dual split-flow catheters was secured at the operative sites before skin closure. A spring-loaded disposable pump then infused 0.25% bupivacaine at a rate of 2.08 cc per catheter per hour for 48 continuous hours. Patient pain levels, nausea/emesis, and oral and intravenous narcotic use were then recorded at 12-hour intervals. Medication use was converted to pain units for results comparison (one pain unit was defined as the equivalent of 10 mg of intravenous morphine). A retrospective control group comprised 16 consecutive patients from December of 1999 to October of 2002 who underwent the same surgery by the same surgeon using oral and intravenous pain medications. The experimental group demonstrated a more than fivefold decrease in the use of oral and intravenous pain medications compared with the historical controls (6.7 versus 1.7 pain units) (p < 0.001). The overall pain experienced by the catheter patients was nearly twofold less than the pain experienced by those without the catheter (1.8 versus 3.4 on the visual analog pain scale) (p < 0.017). Twenty-eight percent of the experimental group experienced nausea/emesis compared with 61 percent in the control group. No complications occurred with the use of the pain pump catheter. A 48-hour infusion of 0.25% bupivacaine significantly decreases the need for postoperative narcotics and the over-all pain experience in immediate breast reconstruction patients. This effective form of pain control may alleviate patient concerns of postoperative pain and may safely downstage many plastic surgery procedures, such as immediate breast reconstruction, and many cosmetic procedures to same-day status when the primary indication for admission is pain management.     

Stereoselective Synthesis of threo-4,4,4-Trichlorothreonine

threo-4,4,4-Trichlorothreonine was synthesized completely stereoselectively through trans-4-alkoxycarbonyl-5-trichloromethyl-2-oxazoline, which was prepared almost quantitatively by the reaction of 2-isocyano acetate with chloral in the presence of an organic base. Several derivatives of these compounds were also synthesized.

Furthermore, the stereochemistry of the resulting trichlorocompounds was chemically elucidated. The trichlorothreonine was easily converted into threo-threonine by hydrogenation over Pd/C in the presence of NaHCO₈.