Antimicrobial sulfonamides clear latent Kaposi sarcoma herpesvirus infection and impair MDM2-p53 complex formation.

Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8, is the causative agent of Kaposi sarcoma; this malignant angiosarcoma is usually treated with conventional antitumor agents that can control disease evolution, but do not clear the latent KSHV episome that binds to cellular DNA. Some commercial antibacterial sulfonamides were tested for the ability to suppress latent KSHV. Quantitative PCR (qPCR) and cytofluorometry assays were used for detecting both viral DNA and the latency factor LANA (latency-associated nuclear antigen) in BC3 cells, respectively. The capacity of sulfonamides to impair MDM2-p53 complex formation was detected by an enzyme-linked immunosorbent assay method. The analysis of variance was performed according to one-way analysis of variance with Fisher as a post hoc test. Here we show that sulfonamide antibiotics are able to suppress the KSHV latent state in permanently infected BC3 lymphoma cells and interfere with the formation of the MDM2-p53 complex that KSHV seemingly needs to support latency and to trigger tumor cell transformation. These findings detected a new molecular target for the activity of sulfonamides and offer a new potential perspective for treating KSHV-induced lymphoproliferative diseases.

Maternal gut and fetal brain connection: Increased anxiety and reduced social interactions in Wistar rat offspring following peri-conceptional antibiotic exposure.

BACKGROUND: A growing body of evidence indicates that gut microbiota characteristics may be closely related to mental dysfunctions. However, no studies have investigated fetal brain development in relation to the maternal gut microbiota, despite the extensive use of antibiotics in obstetric practice. OBJECTIVE: To determine how periconceptional exposure to SuccinylSulfaThiazole (SST), a non-absorbable antibiotic, can affect behavior in rat offspring. This antibiotic drug has previously been shown to substantially perturb the gut microbiota in rats following a 28-day exposure. METHODS: Female Wistar rats were divided in two groups: control, or exposed during one month before breeding until gestational day 15 to a diet containing 1% SST. We administered behavioral tests to offspring, i.e., open field (post-natal day 20), social interactions (P25), marble burying (P30), elevated plus maze (P35), and prepulse inhibition of the acoustic startle reflex (sensory gating) (P45). RESULTS: Both male and female offspring exposed peri-conceptionally to SST showed reduced social interactions, with a decrease of about half in time spent in social interactions compared to controls, reduced exploration of the open arm by 20% in the elevated plus maze test indicating increased anxiety and altered sensorimotor gating, with a 1.5-2-fold decrease in startle inhibition. CONCLUSION: Maternal periconceptional exposure to SST provokes alterations in offspring behavior in the absence of maternal infection. Because we administered SST, a non-absorbable antibiotic, only to the dam, we conclude that these neurobehavioral alterations in the offspring are related to maternal gut microbiota alterations.

Preliminary evidence of the contribution of the intestinal microflora to biotin supply in zebrafish Danio rerio (Hamilton-Buchanan).

A study was conducted to preliminarily assess the contribution of the intestinal microflora to biotin supply in zebrafish. Biotin and avidin were added to three isonitrogenous and isocaloric purified diets to provide molar avidin: biotin ratios of 0:0 (basal diet), 0:1 (biotin-supplemented diet), and 120:0. Another diet was made by supplementing the antibiotic succinylsulfathiazole (1%, wt/wt) to the basal diet. A fifth diet was the Zeigler commercial diet for zebrafish. Each diet was fed to a triplicate group of fish (mean initial mass 0.266 g) for 8 weeks. The condition factor, feed conversion ratio (FCR), percentage weight gain, and survival were similar in fish groups fed the commercial and the biotin-supplemented diets, but energy conversion efficiency and whole-body biotin content were highest in the fish fed the commercial diet (p<0.05). Reduced growth and survival, and increased FCR were noted in fish fed basal diet compared with those fed biotin-supplemented diet. The supplementation of avidin in diet led to lower survival and condition factor, and higher FCR than that observed with basal diet. Intestinal microbial synthesis is assumed to be a significant source of biotin to the zebrafish, as fish fed the antibiotic-supplemented diet showed the lowest growth, health condition, and feed utilization.

Toxic epidermal necrolysis: a medical student's perspective.

As a third year medical student, I was hospitalized for approximately one month with Toxic Epidermal Necrolysis (TEN). Consequently, I have developed an insight into the role of patient as well as that of medical care giver. My experience prompted an intense interest in this particular adverse drug reaction and research into treatment recommendations. Treatment has changed in recent years and this resulted in significantly improved survival. Steroids, once commonly used, are now considered contraindicated. Because of the wide variety of medications which may be associated with this adverse reaction, it is essential to be familiar with the clinical presentation of TEN, as well as the initial steps in treatment.

Screening prescription drugs for possible carcinogenicity: eleven to fifteen years of follow-up.

Using computerized pharmacy records from 1969 to 1973 for a cohort of 143,574 members of the Kaiser Permanente Medical Care Program, we have been testing associations of 215 drugs or drug groups with subsequent incidence of cancer at 56 sites. This paper presents findings with follow-up through 1984. There were 227 statistically significant (P less than 0.05, two-tailed) associations: 170 positive, 57 negative. Some were undoubtedly chance findings; others were likely due to confounding by unmeasured covariables. However, several associations suggested hypotheses for further studies and/or the need for continued observation. Most notable among findings not previously reported were associations of several antibiotics, both oral and topical, with lung cancer. These associations could not be explained by indications for drug use or by differences in smoking habits between users and nonusers, and suggest a possible link between the occurrence of bacterial infections and risk for cancer. In general, our results continue to suggest that most medications used during that period did not affect cancer incidence substantially. However, for less frequently prescribed medications, our power to detect moderate increases in cancer risk was quite low.

Death from drug-induced hemolytic anemia.

Fatal hemolytic anemia occurred in a 71-year-old man after trimethoprim-sulfamethoxazole was given for presumed cystitis. Administration of this combination has previously caused multiple hematologic reactions by affecting folic acid metabolism. Megaloblastic anemia and neutropenia have been produced by both of these agents, while sulfamethoxazole alone has induced acute hemolytic anemia in patients with hereditary deficiency of glucose-6-phosphate dehydrogenase. Although hematologic complications of trimethoprim-sulfamethoxazole treatment usually follow long-term or high-dose therapy, acute reactions apparently may occur at lower doses as well.

Pulmonary infiltrates and hypoxemia in patients with the acquired immunodeficiency syndrome re-exposed to trimethoprim-sulfamethoxazole.

Fever, hypotension, pulmonary infiltrates, and hypoxemia developed upon re-exposure to trimethoprim-sulfamethoxazole in 2 patients with the Acquired Immunodeficiency Syndrome. This reaction can mimic sepsis or the clinical worsening of underlying pulmonary opportunistic infection. The literature concerning adverse pulmonary effects of trimethoprim-sulfamethoxazole is reviewed.

Otolaryngologic complications of acute porphyria.

The porphyrias are a group of diseases which may be complicated by acute neurological crises having serious morbidity and a high rate of mortality. We report a case of acute porphyria in which an acute neurological crisis, resulting in loss of laryngeal function, precipitated life-threatening aspiration pneumonia.

Multiple attacks of jaundice associated with repeated sulfonamide treatment.

Four women who were treated with sulfonamides because of recurrent urinary tract infections experienced adverse liver reactions with jaundice during their third, fourth and fifth course of treatment, respectively. In spite of this, sulfonamide treatment was reinitiated some years later. Adverse liver reactions with jaundice recurred on all occasions. The clinical picture of the liver reactions was indistinguishable from that of viral hepatitis and a hepatitis-like reaction was also seen histologically. Signs of fibrosis appeared histologically after a third attack of jaundice associated with sulfonamides in one patient, but otherwise no persisting abnormalities were noted.

Adverse drug reactions during treatment of urinary tract infections.

Adverse reactions reported to the Swedish Adverse Drug Reaction Committée concerning Sulfapral (a sulphonamide combination for urinary tract infections) and nitrofurantoin were remarkably similar. The commonest hypersensitivity reactions were in skin and lung. During the 10-year period 1966-75 reactions to the sulphonamide were fewer (n=327) than those reported for nitrofurantoin (n=781), but the former appeared to carry a higher mortality rate - 4.6% of reported sulphonamide reactions were fatal as compared to only 1.0% for nitrofurantoin (P less than 0.001). The number of reactions to the sulphonamide tended to remain constant, whereas those to nitrofurantoin increased rapidly, both absolutely as well as relative to sales of the drug.