Reversible Neurotoxicity Due To Excessive Use of Ethyl Chloride.

BACKGROUND: Ethyl chloride is commercially available as a DVD/VCR cleaner, and can be found as a gasoline additive and topical anesthetic. There is an emerging trend of recreational huffing to enhance sexual relations. Neurotoxicity from repeated abuse is uncommon. CASE REPORT: A 36-year-old man with a history of intermittent ethyl chloride use for 15 years presented to the Emergency Department with an inability to walk for 4 days after frequent use for 1 week. The patient reported a rapid titration of inhalation from zero to eight cans of 4.6 oz ethyl chloride aerosol per day over a 1-week period. Initial vital signs were heart rate 88 beats/min, blood pressure 147/60 mm Hg, temperature 37.2°C (99°F), and respiratory rate 16 breaths/min. Physical examination was notable for slurred speech, ptosis, a wide-based and ataxic gait with short strides, inability to stand without support, loss of toe/finger proprioception, horizontal and vertical nystagmus, and dysmetria on coordination testing. Strength and sensation were preserved. His work-up included computed tomography and magnetic resonance imaging of the brain, cervical, thoracic, and lumbar spine that demonstrated no acute abnormalities. On hospital day 9, the patient was able to ambulate with mild difficulty. WHY SHOULD AN EMERGENY PHYSICIAN BE AWARE OF THIS?: Toxicity from excessive ethyl chloride huffing has been rarely reported. The toxicity was characterized with cerebellar findings, no attributable laboratory abnormalities, and no radiographic abnormalities on computed tomography/magnetic resonance imaging. The neurotoxicity resolved with supportive care. This case of excessive huffing of ethyl chloride presenting with neurotoxicity and ataxia further characterizes a rare complication of ethyl chloride toxicity that is gaining popularity.

Intestinal barrier tightening by a cell-penetrating antibody to Bin1, a candidate target for immunotherapy of ulcerative colitis.

Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) could prevent lesion formation in the colon mucosa in part by preventing rupture of lymphoid follicles. In vivo administration of Bin1 mAb altered tight junction protein expression and cecal barrier function. Strikingly, electrophysiology studies in organ cultures showed that Bin1 mAb could elevate resistance and lower 14 C-mannitol leakage across the cecal mucosa, consistent with a direct strengthening of colonic barrier function. Transcriptomic analyses of colitis tissues highlighted altered expression of genes involved in circadian rhythm, lipid metabolism, and inflammation, with a correction of the alterations by Bin1 mAb treatment to patterns characteristic of normal tissues. Overall, our results suggest that Bin1 mAb protects against UC by directly improving colonic epithelial barrier function to limit gene expression and cytokine programs associated with colonic inflammation.

The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists.

Humans consider themselves discrete autonomous organisms, but recent research is rapidly strengthening the appreciation that associated microorganisms make essential contributions to human health and well being. Each person is inhabited and also surrounded by his/her own signature microbial cloud. A low diversity of microorganisms is associated with a plethora of diseases, including allergy, diabetes, obesity, arthritis, inflammatory bowel diseases, and even neuropsychiatric disorders. Thus, an interaction of microorganisms with the host immune system is required for a healthy body. Exposure to microorganisms from the moment we are born and appropriate microbiome assembly during childhood are essential for establishing an active immune system necessary to prevent disease later in life. Exposure to microorganisms educates the immune system, induces adaptive immunity, and initiates memory B and T cells that are essential to combat various pathogens. The correct microbial-based education of immune cells may be critical in preventing the development of autoimmune diseases and cancer. This review provides a broad overview of the importance of the host microbiome and accumulating knowledge of how it regulates and maintains a healthy human system. Cancer Res; 77(8); 1783-812. ©2017 AACR.

Future Challenges for Vaccinologists.

Vaccination is one of the cheapest health-care interventions that have saved more lives than any other drugs or therapies. Due to successful immunization programs we rarely hear about some of the common diseases of the early twentieth century including small pox and polio. Vaccination programs have also helped to increase food production notably poultry, cattle, and milk production due to lower incidence of infectious diseases in farm animals. Though vaccination programs have eradicated several diseases and increased the quality of life there are several diseases that have no effective vaccines. Currently there are no vaccines for cancer, neurodegenerative diseases, autoimmune diseases, as well as infectious diseases like tuberculosis, AIDS, and parasitic diseases including malaria. Abuse of antibiotics has resulted in the generation of several antibiotic-resistant bacterial strains; hence there is a need to develop novel vaccines for antibiotic-resistant microorganisms. Changes in climate is another concern for vaccinologists. Climate change could lead to generation of new strains of infectious microorganisms that would require development of novel vaccines. Use of conventional vaccination strategies to develop vaccines has severe limitations; hence innovative strategies are essential in the development of novel and effective vaccines.