[Research advances on the clinical characteristics and diagnosis and treatment of autoimmune disease-related ulcers].

Studies have shown that autoimmune disease (AID)-related ulcers are disease complications that lead to serious poor prognosis such as infection and disability. It is difficult to make a clear diagnosis and there are contradictions between the applications of immunosuppressive therapy and anti-infectious therapy. Improper diagnosis and immunosuppressive therapy can easily delay the timing of anti-infectious therapy and surgery for patients, which bring adverse effects on the prognosis of patients. This paper reviews the concept, clinical characteristics and treatment suggestions of each subtype of AID-related ulcers, in order to provide more ideas for AID-related ulcers' clinical diagnosis and treatment.

Synthesis, antiviral activity, and biological properties of vinylacetylene analogs of enviroxime.

A series of vinylacetylene analogs of Enviroxime (1) was synthesized. The new compounds are potent inhibitors of poliovirus in tissue culture. Cross-sensitivity with Enviroxime-derived mutants shows that the new compounds have the same mechanism of action as Enviroxime, which involves the viral 3A protein. In studies with Rhesus monkeys, the p-fluoro derivative 12 was found to be unique in providing oral bioavailability. Metabolism studies using hepatic microsomes suggest that this procedure would be a useful in vitro method for selecting the appropriate animal model for testing oral absorption. Compound 12 was found to be efficacious by oral administration in treating a Coxsackie A21 infection in CD-1 mice.

Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease.

Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide substituents of the inhibitor interact with the S1 and S2 subsites of HIV-1 protease, respectively. In vivo studies indicate that AG1343 is well absorbed orally in a variety of species and possesses favorable pharmacokinetic properties in humans. AG1343 (Viracept) has recently been approved for marketing for the treatment of AIDS.

Nasal drug delivery system of a quaternary ammonium compound: clofilium tosylate.

The blood levels of the [14C]clofilium ion in rats after various routes of administration of clofilium tosylate were compared. The results indicate that the blood levels after nasal administration were not statistically different from levels after intravenous administration (p greater than 0.05). Administration by the oral route resulted in considerably lower blood levels. Nasal administration of clofilium tosylate appeared to be superior to oral administration. Histological examinations of nasal mucosa were conducted. At the lower concentration, mild necrosis was observed, and large areas of mucosa were unaffected. However, necrosis of large areas of mucosa occurred after exposure to the higher concentration. Levels of radioactivity in heart, liver, lung, and kidney tissue, as a function of time, were also studied. Unlike the blood levels after nasal administration, the levels of radioactivity were persistent in heart tissue. The data suggest that the [14C]clofilium ion and/or metabolite concentrate in the heart and that blood levels of radioactivity may not be an accurate index of cardiac levels or biological response.

Nasal delivery of polypeptides I: nasal absorption of enkephalins in rats.

The serum levels of two enkephalins after various routes of administration were compared in rats. The results indicated that serum levels of metkephamid after nasal administration were not significantly different than levels after intravenous injection. The oral administration of metkephamid resulted in undetectable serum levels. The effects of a promoter and variations in the peptide dose on nasal absorption were studied. Depending on the stability of the polypeptide and its susceptibility to enzymatic degradation, nasal absorption of peptides can be influenced by the presence of a promoting agent in the formulation. A linear relationship between the dose and the AUC was observed in the range of concentrations studied. The absorption mechanism appears to be passive diffusion. Microscopic examinations of nasal mucosa in rats revealed degrees of irritation which, considering the experimental exposure, were slight and probably repairable. The data indicate that enkephalins can be absorbed through the nasal mucosa into the systemic circulation, and the onset of absorption was rapid. Nasal administration may offer an attractive alternative for the delivery of proteins and/or polypeptides which are, in general, absorbed poorly when given orally.

Nonaqueous cephalosporin suspension for parenteral administration: cefazolin sodium.

The flocculation-deflocculation behavior of cefazolin sodium (I) in nonaqueous media and the effect of surfactants as measured by zeta potential, sedimentation, and porosity were studied. A significant difference in zeta potential was observed when the particles were suspended in different nonaqueous media. The addition of surfactant produced a deflocculated state. The surfactant deflocculated the particles by a process of supersaturation and crystallization involving a surfactant-cefazolin complex. The shielding effect of the surfactant on the surface of the particles also apparently affected their electrophoretic properties. Kinetic studies on the stability of the drug as a function of temperature were conducted; it appears that the chemical stability in ethyl oleate at room temperature is adequate for a reasonable shelf life. The efficiency of absorption of the drug from the ethyl oleate suspension was evaluated after intramuscular administration in dogs. The area under the plasma concentration versus time curve and urinary recovery indicated that cefazolin was 100% bioavailable from this nonaqueous preparation.

[Mediastinal mass and anesthesia in children--a case report].

A three-year-old girl with mediastinal mass received right exploratory thoracotomy was reported. The mediastinal mass of this patient occupied the whole right lung and compressed the right main bronchus as confirmed by X-ray and CT of the chest. For mediastinal mass surgery, several fatal hazards can happen during induction of anesthesia, maintenance and even the post-operative period. The two main hazards are trachobronchial obstruction and cardiovascular collapse. We presented our experience of this case including preparation, planning, induction technique, maintenance of anesthesia and postoperative care. We hoped that this can help others to minimize accidents when they handle patients with similar conditions.

[Pre- and intra-operative administration of epidural morphine provides good postoperative pain relief after laminectomy].

BACKGROUND: To evaluate the postoperative analgesic effect of epidural morphine administered at different timing in lumbar spine surgery. METHODS: Eighty-four patients who were scheduled for elective lumbar spine surgery were randomized in three groups. Seventeen patients in group I who received non-steroid analgesics postoperatively (diclophenac sodium 50 mg, iv, q4h) served as control while thirty-six patients in group II who received single dose epidural morphine 3 mg in combination with 10 ml 2% lidocaine given at the lesion site (L4-5 or L5-S1) just before general anesthesia and thirty-one patients in group III who received 3 mg morphine in combination with 3 ml 2% lidocaine administered to the targeted epidural space by means of slow drippings just before wound closure were studied subjects. RESULTS: During the first 24 h postoperatively, the patients in group II and group III suffered a pain which was significantly less in intensity as compared with those in group I (p < 0.05). We used the 10 cm visual analog pain score (VAS) to scale post-operative pain with "no pain" and "worst pain" respectively anchored at 0 and 10 cm. The incidence of side effects such as pruritus, nausea and vomiting was higher in group II and III than in group I. We did not evaluate the occurrence of urinary retention because routine retention urinary catheterization in all patients hampered us to do so. There were no significant differences in the quality and duration of analgesia between group II and III. Respiratory depression of clinical significance was not observed. Neither decrease in oxygen saturation below 92% registered on pulse oximetry nor decrease in respiratory rate below 12 cycles/min was found in the PACU. CONCLUSIONS: Preoperative or intraoperative administration of epidural morphine could provide satisfactory analgesia in lumbar spine surgery during the first 24 h postoperatively.

[Disseminated intravascular coagulation--a case report].

A 31 year-old T1PoAoL1 female developed the early Disseminated Intravascular Coagulation (DIC) signs after cesarean section. The patient had recovery completely after transabdomen total hysterectomy (TAH) and blood products transfusion. Case presentation, literature review, possible pathogenetic mechanism and treatment of DIC were discussed.