Perinatal exposure to benzyl butyl phthalate induces alterations in neuronal development/maturation protein expression, estrogen responses, and fear conditioning in rodents.

Phthalate exposure has recently been associated with behavioral actions that are linked to its endocrine-disrupting properties. The purpose of this study was to investigate the molecular, anatomical, and behavioral effects of indirect perinatal benzyl butyl phthalate (BBP) exposure in offspring of BBP-treated pregnant dams. In two separate experiments, we administered BBP (10.0 µg/ml) on food pellets to pregnant dams and examined the offspring. The first experiment revealed reproductive anatomical abnormalities linked to BBP's endocrine-disrupting properties, whereas histological analysis revealed preserved hippocampal neuronal migration. The second experiment demonstrated learning and memory impairments accompanied by molecular abnormalities in multiple brain regions. Offspring from BBP-treated dams had altered levels of several proteins important for neuronal circuitry formation, tissue development, and maturation. We suggest that BBP administration disrupts normal learning and that these effects could be related to alterations in brain development and result in a phenotype similar to that observed in neurodevelopmental disorders.

Chronic exposure to benzyl butyl phthalate (BBP) alters social interaction and fear conditioning in male adult rats: alterations in amygdalar MeCP2, ERK1/2 and ERα.

OBJECTIVES: Benzyl Butyl Phthalate (BBP) is an industrial plasticizer that has an unknown action in the central nervous system. Phthalates have recently been associated with behavioral actions that are linked to their endocrine disrupting properties. The purpose of this study was to investigate the behavioral and molecular effects of BBP treatment in male rats. DESIGN: Male rats were chronically exposed to BBP in the drinking water (5.0 ppm and 10.0 ppm) throughout adolescence and into the adult phase of life. Their behavior was then assessed in a learning and memory task (fear conditioning), open field exploration and a test of sociability. RESULTS: BBP treated rats showed decreased freezing in fear conditioning, no changes in open field exploration, and increased aberrant social behavior. Rats were sacrificed at post natal day 140 and blood and brains were harvested and processed. We found increased hormonally active estrogen, 17-ß estradiol, in the serum of BBP treated rats. BBP treatment also induced changes in amygdalar proteins related to synaptic plasticity including decreased MeCP2 levels that correlated with tests of sociability with no changes in stress related proteins such as nuclear factor kappa B (NFkB). We also found alterations in physiological responses as measured by body weight without changes in food consumption suggesting disruption of metabolism and body homeostasis. CONCLUSIONS: We suggest that BBP administration disrupts normal learning and social behavior, and that these effects could be related to alterations of amygdala function.

Statin-Induced Autoimmune Necrotizing Myopathy.

Statin therapy is a widely prescribed medication class for hypercholesterolemia. In statin-induced autoimmune myopathy, genetically predisposed and at-risk patients can develop antibodies against hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the key enzyme in the production of cholesterol. As a result, an autoimmune reaction causing weakness, myalgia, with possible severe rhabdomyolysis, renal failure, and myonecrosis also can occur. A 73-year-old female presented to clinic with myalgia and fatigue. She was on atorvastatin 20 mg/day for over 1 year, which she stopped 1 week prior to her initial presentation. Patient did experience rhabdomyolysis as well as a transaminitis. She underwent an autoimmune workup which was positive for HMG-CoA reductase antibodies. Patient was initially treated on a prednisone taper, starting dose 50 mg/day. Without remission of symptoms, methotrexate 15 mg/week was initiated.

Seronegative Arthritis as a Complication of Whipple's Disease.

Whipple's disease (WD) is an uncommon cause of seronegative arthritis. WD is known for its gastrointestinal symptoms of diarrhea, weight loss, and abdominal pain. However, arthritis may precede gastrointestinal symptoms by 6 to 7 years. We describe a case of an 85-year-old Caucasian male with multiple joint complaints, not responsive to traditional treatments for conditions such as rheumatoid arthritis and osteoarthritis. We suggest that WD be considered for seronegative arthritis especially affecting large joints.

Amiodarone-Associated Myxedema Coma.

BACKGROUND Myxedema coma is an uncommon severe thyroid disorder that is fatal in 25-60% of cases. Although the differential diagnosis for altered mental status is extensive, including many more common causes such as infection, medication changes, electrolyte abnormalities, and exacerbation of chronic illnesses, profound hypothyroidism is an uncommon cause that can be overlooked. CASE REPORT We describe the case of a 71-year-old man on long-term amiodarone treatment for atrial fibrillation who presented with altered mental status initially ascribed to uremia, hyponatremia, and pneumonia. When his mental status did not resolve, thyroid tests showed his thyroid-stimulating hormone level was 89 µIU/mL, along with clinical criteria for myxedema coma. CONCLUSIONS We suggest that thyroid function tests should be considered in encephalopathic older adults on amiodarone.