Surface modification of electrospun PLGA scaffold with collagen for bioengineered skin substitutes.

In skin tissue engineering, surface feature of the scaffolds plays an important role in cell adhesion and proliferation. In this study, non-woven fibrous substrate based on poly (lactic-co-glycolic acid) (PLGA) (75/25) were hydrolyzed in various concentrations of NaOH (0.05N, 0.1N, 0.3N) to increase carboxyl and hydroxyl groups on the fiber surfaces. These functional groups were activated by EDC/NHS to create chemical bonding with collagen. To improve bioactivity, the activated substrates were coated with a collagen solution (2mg/ml) and cross-linking was carried out using the EDC/NHS in MES buffer. The effectiveness of the method was evaluated by contact angle measurements, porosimetry, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), tensile and degradation tests as well as in vitro cell attachment and cytotoxicity assays. Cell culture results of human dermal fibroblasts (HDF) and keratinocytes cell line (HaCat) revealed that the cells could attach to the scaffold. Further investigation with MTT assay showed that the cell proliferation of HaCat significantly increases with collagen coating. It seems that sufficient stability of collagen on the surface due to proper chemical bonding and cross-linking has increased the bioactivity of surface remarkably which can be promising for bioengineered skin applications.

Results of a double-blind placebo-controlled study of the double-stranded RNA drug polyI:polyC12U in the treatment of HIV infection.

In this multicenter, randomized, double-blind study the activity of polyI:polyC12U administered with zidovudine was evaluated in the treatment of HIV infection. Thirty-six HIV-positive, pre-AIDS individuals (100-500 CD4+ cells/mm3) who had had at least six months of zidovudine therapy received polyI:polyC12U (400 or 700 mg) or placebo twice weekly with zidovudine. PolyI:polyC12U subjects with baseline CD4+ counts > or = 300/mm3 showed a trend towards reduced CD4+ loss versus placebo recipients. PolyI:polyC12U subjects were more likely to exhibit positive delayed-type hypersensitivity responses than placebo recipients. Placebo subjects crossing over to polyI:polyC12U therapy demonstrated improved CD4+ and delayed-type hypersensitivity responses. PolyI:polyC12U subjects with baseline CD4+ counts > or = 300/mm3 were less likely to develop AIDS than similar placebo subjects. PolyI:polyC12U therapy of HIV-positive subjects restored or stabilized immune function as indexed by delayed-type hypersensitivity reactivity and, in individuals with CD4+ counts > 300/mm3, abrogated CD4+ loss and reduced disease progression. PolyI:polyC12U was generally well-tolerated in this zidovudine-treated population. No subject discontinued therapy due to an adverse reaction or aberrant laboratory parameter.

Cephalosporins: rationale for clinical use.

Cephalosporins, the most widely used class of antibiotics, are more resistant than penicillins to inactivation by beta-lactamases. Based on their spectrum of activity against gram-negative bacteria, cephalosporins are classified into three generations. The generation classification, however, does not correlate with activity against gram-positive bacteria or anaerobes. First-generation cephalosporins have a narrow gram-negative spectrum but are most active against gram-positive bacteria, particularly Staphylococcus aureus. Third-generation compounds have excellent activity against gram-negative bacteria. The cephamycins, a second-generation subgroup that includes cefoxitin, cefotetan and cefmetazole, have the best activity against anaerobes.

Zidovudine for the treatment of HIV infection.

Zidovudine, the first widely used antiretroviral agent, prevents replication of the human immunodeficiency virus (HIV) by inhibiting reverse transcriptase. Its use in patients with acquired immunodeficiency syndrome slows progression of the disease and prolongs survival. Zidovudine also significantly reduces the rate of progression to AIDS in adults with asymptomatic HIV infection and CD4 T-lymphocyte counts below 500 per mm3. The major toxicity of the drug is bone marrow suppression resulting in anemia or granulocytopenia, or both. Recently, lower doses have been shown to be effective and are associated with less toxicity.

Pentamidine for the prevention and treatment of P. carinii pneumonia.

Pentamidine is effective in both the treatment and the prevention of Pneumocystis carinii pneumonia. The agent may be administered by slow intravenous infusion or aerosol, although intravenous therapy is associated with a wide range of adverse reactions, including nephrotoxicity, hypoglycemia and neutropenia. Toxic effects may occur in up to 25 percent of patients.

Clostridial endocarditis. Report of a case caused by Clostridium bifermentans and review of the literature.

A case of Clostridium bifermentans endocarditis occurred in a 23-year-old man who was an intravenous drug user. There was no history of preexisting valvular heart disease. He was initially treated with high-dose penicillin G potassium but remained bacteremic for a ten-day period. The bacteremia resolved when the therapy was changed to metronidazole hydrochloride. A review of the 16 reported cases of clostridial endocarditis showed no predisposing host factor to the development of the disease. Penicillin is the treatment of choice for clostridial endocarditis, but metronidazole should be considered as an alternate therapy for treatment that fails.

Necrotizing fasciitis in adults due to group B streptococcus. Report of a case and review of the literature.

Necrotizing fasciitis is an uncommon severe infection involving subcutaneous tissues and advancing along fascial planes. Group B streptococcal infections occur disproportionately in diabetics and pregnant women. Although fasciitis secondary to group B streptococcus has been described in infants and adult women in the postpartum period, we report the first case, to our knowledge, of group B streptococcal necrotizing fasciitis in an adult diabetic unrelated to obstetric complications.

Efficacy and safety of aztreonam in the treatment of serious gram-negative bacterial infections.

Aztreonam was used in the initial treatment of infection of the urinary tract (23 cases), respiratory tract (17 cases), skin and soft tissue (12 cases), abdominal cavity (three cases), endocarditis (two cases), septicemia (eight cases), and osteomyelitis (two cases). In 26 of 60 evaluable infectious episodes, aztreonam was used alone. Clinical cure was observed in 35 of 60, improvement in 24 of 60, and failure in one of 60 cases. Ten patients developed subsequent superinfection. Aztreonam was well tolerated, although one case of exfoliative dermatitis and one of pseudomembranous colitis occurred. However, these cases were complicated by proximal administration of other antibiotics.

Gram-negative bacillary meningitis.

The incidence of gram-negative bacillary meningitis has increased significantly in the past two decades. Approximately two thirds of all reported cases have occurred after neurosurgical procedures. With the development of the newer cephalosporins, the overall mortality rate has decreased from 40 to 80 per cent to 10 to 20 per cent.

Tuberculous meningitis.

Tuberculous meningitis arises from the discharge of bacilli from a subjacent caseous focus into the subarachnoid space. Meningeal involvement is most marked at the base of the brain. The clinical spectrum is very broad and the outcome of therapy depends mainly on the stage of disease at the time treatment is instituted.

Effectiveness of cefotaxime in gram-negative meningitis.

We treated 12 adult patients who had gram-negative bacillary meningitis with cefotaxime administered intravenously at a dose of 2 g every 4 hours. The etiological organisms included Haemophilus influenzae (3 cases), Serratia marcescens (3 cases), Klebsiella pneumoniae (3 cases), Escherichia coli (2 cases), and Enterobacter (1 case). The infection followed a neurosurgical procedure in 6 cases. The mean inhibitory and bactericidal concentrations of cefotaxime for the isolates ranged from 0.125 to 0.25 microgram/ml. The cerebrospinal fluid (CSF) concentrations of cefotaxime ranged from 5.0 to 15.2 micrograms/ml, and the CSF bactericidal titers were 1:64 to 1:128. The CSF in all patients was sterilized within 96 hours. All 12 patients recovered, and there were no relapses.

Cefmenoxime. Clinical, bacteriologic, and pharmacologic studies.

Cefmenoxime, a new semisynthetic third-generation cephalosporin, was evaluated in 105 patients (45 men and 60 women) with the following infections: skin or skin structure (33), pulmonary (22), urinary tract (30), and septicemia (20). Forty-two infections were hospital-acquired, 85 patients had underlying diseases, 29 patients required concomitant surgery, and 32 patients had positive results of blood culture. Cefmenoxime dosages ranged from 4 to 12 g per day intravenously for one and a half to 51 days. Cultures revealed 183 organisms in the 105 patients. Minimal inhibitory concentrations were obtained for cefmenoxime, cefoperazone, cefotaxime, cefamandole, cefoxitin, and moxalactam. Cefmenoxime and cefotaxime exhibited nearly equivalent activities against all organisms tested and were the most active agents tested against all aerobic and facultative organisms except Staphylococcus aureus. Mean serum peak and trough levels obtained after 2 g every six hours were 84.1 micrograms/ml (peak), 8.3 micrograms/ml (trough); and after 2 g every four hours, 106 micrograms/ml (peak) and 10.9 micrograms/ml (trough). Of 105 infections, 86 were clinically cured, three were not cured, and 16 were not evaluable. Safety studies revealed 24 transient reactions in 23 patients including eosinophilia, diarrhea, leukopenia, rash, elevated liver enzyme levels, Antabuse effect, and phlebitis. On the basis of these clinical and in vitro results, cefmenoxime is a safe drug for the treatment of infections caused by gram-negative and gram-positive aerobic organisms.