Bioenergetics dysfunction, mitochondrial permeability transition pore opening and lipid peroxidation induced by hydrogen sulfide as relevant pathomechanisms underlying the neurological dysfunction characteristic of ethylmalonic encephalopathy.

Hydrogen sulfide (sulfide) accumulates at high levels in brain of patients with ethylmalonic encephalopathy (EE). In the present study, we evaluated whether sulfide could disturb energy and redox homeostasis, and induce mitochondrial permeability transition (mPT) pore opening in rat brain aiming to better clarify the neuropathophysiology of EE. Sulfide decreased the activities of citrate synthase and aconitase in rat cerebral cortex mitochondria, and of creatine kinase (CK) in rat cerebral cortex, striatum and hippocampus supernatants. Glutathione prevented sulfide-induced CK activity decrease in the cerebral cortex. Sulfide also diminished mitochondrial respiration in cerebral cortex homogenates, and dissipated mitochondrial membrane potential (ΔΨm) and induced swelling in the presence of calcium in brain mitochondria. Alterations in ΔΨm and swelling caused by sulfide were prevented by the combination of ADP and cyclosporine A, and by ruthenium red, indicating the involvement of mPT in these effects. Furthermore, sulfide increased the levels of malondialdehyde in cerebral cortex supernatants, which was prevented by resveratrol and attenuated by glutathione, and of thiol groups in a medium devoid of brain samples. Finally, we verified that sulfide did not alter cell viability and DCFH oxidation in cerebral cortex slices, primary cortical astrocyte cultures and SH-SY5Y cells. Our data provide evidence that bioenergetics disturbance and lipid peroxidation along with mPT pore opening are involved in the pathophysiology of brain damage observed in EE.

Pigmented purpuric dermatosis after taking a dietary supplement.

Pigmented purpuric dermatoses (PPDs) are a group of histologically similar skin eruptions characterized by a perivascular lymphocytic infiltrate with extravasated erythrocytes. The etiologies of these conditions are unknown, but triggering factors such as systemic diseases, infections, drugs, and foods have been described. Here, we present a patient who developed pigmented purpura 30 days after initiating a dietary supplement that contained selenium, natural vitamin E, and a parsley concentrate, specifically, Parselenium E. One month after stopping the dietary supplement, the lesions disappeared and no new lesions have developed.

Acute scurvy during treatment with interleukin-2.

The association of vitamin C deficiency with nutritional factors is commonly recognized. However, an acute form of scurvy can occur in patients with an acute systemic inflammatory response, which is produced by sepsis, medications, cancer or acute inflammation. The frequency of acute hypovitaminosis C in hospitalized patients is higher than previously recognized. We report the occurrence of acute signs and symptoms of scurvy (perifollicular petechiae, erythema, gingivitis and bleeding) in a patient hospitalized for treatment of metastatic renal-cell carcinoma with high-dose interleukin-2. Concomitantly, serum vitamin C levels decreased to below normal. Better diets and longer lifespan may result a lower frequency of acute scurvy and a higher frequency of scurvy associated with systemic inflammatory responses. Therefore, increased awareness of this condition can lead to early recognition of the cutaneous signs of acute scurvy in hospitalized patients with acute illnesses or in receipt of biological agents, and prevent subsequent morbidity such as bleeding, anaemia, impaired immune defences, oedema or neurological symptoms.

Oral mucosal lesions, microbial changes, and taste disturbances induced by adjuvant chemotherapy in breast cancer patients.

OBJECTIVE: The aim of the study was to examine oral mucosal lesions, microbial changes, and taste disturbances induced by adjuvant chemotherapy (CT) in breast cancer patients during and 1 year after treatment. STUDY DESIGN: Forty-five consecutive breast cancer patients, eligible for adjuvant CT with cyclophosphamide, epirubicin or methotrexate, and 5-fluorouracil were followed before, during, 6 months and 1 year after CT and were compared to a control group of 31 breast cancer patients not receiving adjuvant CT. RESULTS: During CT, oral mucosal lesions developed including erythema (n = 10, 22%) and ulceration (n = 7, 16%). Five patients (11%) were diagnosed with oral candidosis. Scores of dental bacterial plaque and gingival inflammation increased during CT and the oral microbial composition changed towards a more acidophilic flora. Taste disturbances were experienced by 84% (n = 38) of the patients in the CT group. CONCLUSION: In breast cancer patients, moderate-intensive adjuvant CT caused oral mucosal lesions, oral candidosis, taste disturbances and a more acidophilic oral microflora. These adverse effects were temporary and the majority of the patients were mildly affected.

Photolocalized purpura during ciprofloxacin therapy.

Photosensitivity reactions reported with ciprofloxacin mimic those of sunburn, with erythema and edema in the milder forms, and painful blistering with subsequent peeling when severe. Purpuric eruptions during treatment with ciprofloxacin have been rarely reported. We describe a 30-year-old man who was given a 15-day course with ciprofloxacin 500 mg twice a day for a prostatitis. Coinciding with sun exposure, he developed a purpuric, pruriginous eruption on his lower extremities, consisting of erythematous, petechial lesions located on the anterior aspect of his thighs and legs, clearly delimited by his bathing suit. The lesions cleared completely after the discontinuation of the drug and treatment with topical clobetasol. The acute reaction observed in our patient differed from a classical sunburn, consisting of confluent petechias, strictly limited to sunlight-exposed areas, and accompanied by pruritus. Photoexposed purpuric eruptions should be considered as another side effect of ciprofloxacin therapy in addition to phosensitivity rashes.

Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases.

The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied. These patients, who presented with bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins, were refractory to vitamin K1 at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K1 were used. Metabolic studies demonstrated a blockade in vitamin K utilization, consistent with the presence of a vitamin K antagonist, but the patients denied use of anticoagulants. Warfarin assays were negative. We show that the factitious purpura in each patient was due to the surreptitious ingestion of brodifacoum, a potent second generation long-acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term therapy with large doses of vitamin K1. The serum elimination half-time for brodifacoum ranged from 16 to 36 days in these patients. The anticoagulant effect is of long duration, requiring chronic vitamin K treatment. With increasing availability of new rodenticides, factitious purpura due to surreptitious ingestion of these potent vitamin K antagonists is emerging as a new problem, previously associated with warfarin, with important implications for diagnosis and treatment.

[Complications of lymphography. A propos of 5 cases]. / Complications de la lymphographie. A propos de cinq observations

Complications noted following lymphography have been published by several authors. The authors report here a series of 5 cases occurring in patients with mediastinal and lung cancer. They report the various clinical manifestations resembling fat embolism, the free interval and general signs, pulmonary, neurological, hematological and dermatological symptoms associated with inconstant laboratory abnormalities which permit one to suggest a complex pathogenesis: --Immuno-allergic (early shock due to circulating antibodies). --Mechanical and vascular: incomplete removal of low viscosity lipiodol by the pulmonary macrophage system permits liberation of micro-vascular emboli. --By abnormality of blood coagulation and the onset of a syndrome of widespread intravascular coagulation. Better recognition of the pathogenesis associated with the development of new therapeutic principles, should permit better prevention and control of these complications.