Chronic acidosis rewires cancer cell metabolism through PPARα signaling

The mechanisms linking tumor microenvironment acidosis to disease progression are not understood. Here, we used mammary, pancreatic, and colon cancer cells to show that adaptation to growth at an extracellular pH (pH_e) mimicking acidic tumor niches is associated with upregulated net acid extrusion capacity and elevated intracellular pH at physiological pH_e, but not at acidic pH_e. Using metabolic profiling, shotgun lipidomics, imaging and biochemical analyses, we show that the acid adaptation-induced phenotype is characterized by a shift toward oxidative metabolism, increased lipid droplet-, triacylglycerol-, peroxisome content and mitochondrial hyperfusion. Peroxisome proliferator-activated receptor-α (PPARA, PPARα) expression and activity are upregulated, at least in part by increased fatty acid uptake. PPARα upregulates genes driving increased mitochondrial and peroxisomal mass and β-oxidation capacity, including mitochondrial lipid import proteins CPT1A, CPT2 and SLC25A20, electron transport chain components, peroxisomal proteins PEX11A and ACOX1, and thioredoxin-interacting protein (TXNIP), a negative regulator of glycolysis. This endows acid-adapted cancer cells with increased capacity for utilizing fatty acids for metabolic needs, while limiting glycolysis. As a consequence, the acid-adapted cells exhibit increased sensitivity to PPARα inhibition. We conclude that PPARα is a key upstream regulator of metabolic changes favoring cancer cell survival in acidic tumor niches.     

Non-mechanical traumatic gas gangrene: forgotten but not gone

We report a case of gas gangrene (GG) in a non-diabetic HIV seronegative man who died within 60 hours following an intramuscular injection in rural India. The occurrence of GG after intramuscular injection is rare and only a few cases have been reported in the published literature.     

Ventricular fibrillation after exposure to air freshener-death just a breath away

A case of ventricular fibrillation due to butane toxicity after unintentional inhalation of air freshener is reported for its rarity and to create awareness among practitioners and the public. A 25-year-old woman collapsed in the supermarket after unintended exposure to air freshener sprayed into her nostrils. Her husband started cardiopulmonary resuscitation immediately, and she was brought to the hospital. She had coarse ventricular fibrillation. Defibrillation with 360 J was given, and the rhythm reverted to normal sinus rhythm after the third shock. Epinephrine was not administered, and she was treated with esmolol infusion for ventricular ectopy. The patient recovered completely without any sequelae and was discharged on the fifth hospital day. On thin layer chromatography, the chemical content of the spray was identified to be isobutane. Avoiding epinephrine and administering β-adrenergic blockers may protect the catecholamine-sensitized heart early during resuscitation in butane exposure cases.     

Epithelial cell renewal and turnover and relationship to morphologic abnormalities in jejunal mucosa in tropical sprue

A morphometric study confirmed that increasing severity of the jejunal mucosal morphologic lesion is accompanied by increased crypt height and reduced villus length in patients with tropical sprue. Mitotic activity in the crypts was increased. Pulse labeling of jejunal mucosal biopsies cultured in vitro with [3H]thymidine confirmed that there was increased uptake of label in tropical sprue with more rapid migration of labeled cells to the villi. The label was also lost more rapidly. Earlier ultrastructural studies have shown enterocyte damage and extrusion in the crypt and villus epithelium. The present data suggest that in the jejunal mucosa of patients with tropical sprue, the loss of damaged enterocytes leads to villus shortening and increased cell production in the crypts, with hypertrophy of the crypts.     

Prevalence of intestinal parasitic infestation in HIV/AIDS patients with diarrhea in Madurai City, South India

The prevalence and pattern of parasitic infestation among 80 HIV/AIDS patients with diarrhea in Madurai, south India, was studied by microscopy. Eighty HIV-negative patients were used as controls. Intestinal parasites were detected in 31 HIV/AIDS patients (38.7%) and in 14 (17.5%) HIV-negative patients, a difference that was statistically significant (P < 0.05). In HIV/AIDS patients with diarrhea, protozoa accounted for the majority of diarrhea cases (Entamoeba spp. 37.5%, Cryptosporidium parvum 28.7%). It is therefore suggested that enteric infections are more common in HIV-infected patients than in HIV-negative persons in south India, and this may be due to differences in immunological profile, susceptibility as well as factors related to sanitation and the environment.