Minocycline Hydrochloride Hyperpigmentation Complicating Treatment of Pyoderma Gangrenosum

Minocycline-associated hyperpigmentation is an uncommon side effect We report the case of a patient with pyoderma gangrenosum successfully treated with oral minocycline but complicated by marked hyperpigmentation in his pyoderma gangrenosum and acne scars. One of the clinical forms of minocycline hyperpigmentation includes dark-blue or black macules in depressed acne scars or other sites of skin inflammation; this pattern seems to be independent of the total cumulative dose and the skin process.     

Results of a randomized study of early stage Hodgkin's disease using ABVD,EBVD, or MBVD

From January 1986 to December 1989, 157 previously untreated patients, with Hodgkin's disease stage I or II without bulky disease, were enrolled in a clinical comparative study. The objectives of the study were to compare the efficacy and safety of using epirubicine or mitoxantrone instead of adriamycin in the combination chemotherapy regimen ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The complete response rate was better in the patients treated with the ABVD or EBVD regimens compared to the MBVD arm. Also, differences in overall survival and relapse-free survival were better in the patients who received ABVD or EBVD compared to the MBVD regimen. Hematological, gastrointestinal and cardiac toxicity were similar in the three groups. Dose intensity, delays and complications were also similar in the three groups. The mitoxantrone-containing regimen was found to have less efficacy in comparison to the other regimens tested in the present study in patients with favorable stage I or II Hodgkin's disease. © 1995 Wi1ey-Liss Inc.     

Morphologic Study of the Participation of the Complement System in Hyperacute Rejection of Renal Xenotransplants

The role of polymorphonuclear leukocyte (PMN) and platelet infiltration in the hyperacute rejection of renal xenotransplants was studied. In a first group, a dog kidney was grafted to rabbit recipients with intact immune adherence and chemotaxis. A second group included recipients depleted of PMN's with nitrogen mustard, and in a third group, immune adherence and chemotaxis were modified by depleting the third component of complement by means of cobra venom factor. Serial kidney biopsies were studied with light and electron microscopic technics. A semiquantitative evaluation of PMN and platelet glomerular infiltration indicated that a reduction in the number of PMN's or platelets is associated with an increased survival time of the transplanted kidney.     

Lessons from studies of antigen-specific T cell responses in Multiple Sclerosis

Multiple Sclerosis (MS) is considered a T cell-mediated autoimmune disease of central nervous system myelin. Based on elegant experiments in an animal model of MS, experimental allergic encephalomyelitis (EAE), a number of myelin proteins and peptides derived from these can induce inflammatory demyelinating lesions. Recent studies with transgenic mice expressing human HLA-DR molecules and a myelin basic protein (MBP)-specific T cell receptor as well as data from a phase II clinical trial with an altered peptide ligand based on MBP peptide (83-99) provide convincing evidence that the pathogenetic concepts which largely stem from the above EAE studies are valid in MS, too.     

Structural and biological characterization of three novel mastoparan peptides from the venom of the neotropical social wasp Protopolybia exigua (Saussure).

The venom of the Neotropical social wasp Protopolybia exigua(Saussure) was fractionated by RP-HPLC resulting in the elution of 20 fractions. The homogeneity of the preparations were checked out by using ESI-MS analysis and the fractions 15, 17 and 19 (eluted at the most hydrophobic conditions) were enough pure to be sequenced by Edman degradation chemistry, resulting in the following sequences: Protopolybia MPI I-N-W-L-K-L-G-K-K-V-S-A-I-L-NH2 Protopolybia-MP II I-N-W-K-A-I-I-E-A-A-K-Q-A-L-NH2 Protopolybia-MP III I-N-W-L-K-L-G-K-A-V-I-D-A-L-NH2 All the peptides were manually synthesized on-solid phase and functionally characterized. Protopolybia-MP I is a hemolytic mastoparan, probably acting on mast cells by assembling in plasma membrane, resulting in pore formation; meanwhile, the peptides Protopolybia-MP II and -MP III were characterized as a non-hemolytic mast cell degranulator toxins, which apparently act by virtue of their binding to G-protein receptor, activating the mast cell degranulation.     

Varicella zoster virus in health care workers in northern Israel: seroprevalence and predictive value of history of varicella infection

Health care workers (HCWs) are susceptible to hospital acquired varicella zoster virus (VZV). We evaluated seroprevalence and predictive value of a history of varicella disease (VD) with VZV serology in HCWs in northern Israel. A total of 200 HCWs were enrolled. A high rate of seropositivity for VZV-IgG was found: 98.5% seropositive and only 1.5% seronegative. A positive history of VD was an excellent predictor for the presence of VZV-IgG; however, a negative history of VD does not rule out the presence of VZV-IgG.     

Population Pharmacokinetic Modeling to Describe the Total Plasma and Free Brain Levels of Fluconazole in Healthy and <Emphasis Type="BoldItalic">Cryptococcus neoformans</Emphasis> Infected Rats: How Does the Infection Impact the Drug’s Levels on Biophase?

Purpose

The present work aimed to evaluate the influence of experimental meningitis caused by C. neoformans on total plasma and free brain concentrations of fluconazole (FLC) in Wistar rats.

Method

The infection was induced by the administration of 100 μL of inoculum (1.10⁵ CFU) through the tail vein. Free drug in the brain was assessed by microdialisys (μD). Blood and μD samples were collected at pre-determined time points up to 12 h after intravenous administration of FLC (20 mg/kg) to healthy and infected rats. The concentration-time profiles were analyzed by non-compartmental and population pharmacokinetics approaches.

Results

A two-compartmental popPK model was able to simultaneously describe plasma and free drug concentrations in the brain for both groups investigated. Analysis of plasma and μD samples showed a better FLC distribution on the brain of infected than healthy animals (1.04?±?0.31 vs 0.69?±?0.14, respectively). The probability of target attainment was calculated by Monte Carlo simulations based on the developed popPK model for 125 mg/kg dose for rats and 400–2000 mg for humans.

Conclusions

FLC showed a limited use in monotherapy to the treatment of criptoccocosis in rats and humans to value of MIC >8 μg/mL.