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Context: Despite the great mortality and morbidity of stroke, treatment options remain limited. We previously showed that JM-20, a novel synthetic molecule, possessed a strong neuroprotective effect in rats subjected to transient middle cerebral artery occlusion. However, to verify the robustness of the pre-clinical neuroprotective effects of JM-20 to get good prognosis in the translation to the clinic, it is necessary to use other experimental models of brain ischemia. Aims: To evaluate the neuroprotective effects of JM-20 following the onset of permanent focal cerebral ischemia induced in rats by thermocoagulation of blood into pial blood vessels of cerebral cortices. Methods: Ischemic lesion was induced by thermocoagulation of blood into pial blood vessels of primary motor and somatosensory cortices. Behavioral performance was evaluated by the cylinder testing for a period of 2, 3 and 7 days after surgery, and was followed by histopathological study in brain cortex stained with hematoxylin- eosin. Results: Ischemic injury resulted in impaired function of the forelimb evidenced by high asymmetry punctuation, and caused histopathological alterations indicative of tissue damage at cerebral cortex. JM-20 treatment (4 and 8 mg/kg) significantly decreased asymmetry scores and histological alterations with a marked preservation of cortical neurons. Conclusions: The effects of permanent brain ischemia were strongly attenuated by JM-20 administration, which expands and improves the current preclinical data of JM-20 as neuroprotector against cerebral ischemia, and strongly support the examination of its translation to the clinic to treat acute ischemic stroke.

Context: Pharmacological properties of mangiferin have been reported, but few studies have investigated mangiferin toxicity. Aims: To study the acute and 28-day toxicity effects of mangiferin in rodents. Methods: Single doses of mangiferin were administered by oral or i.p. route or were applied dermally to Sprague-Dawley rats and Balb/C mice. Clinical symptoms of animals were observed during 14 days after treatment. Animals also received single oral doses daily for 28 consecutive days. Blood biochemistry, hematology and pathology findings were reported. Results: In the acute study, no toxic effects were observed after dermal exposure to mangiferin 2000 mg/kg but transient dyspnea, flank position and piloerection were observed after oral administration to this xanthone. I.p. administration induced similar toxicity signs, but at the highest dose (2000 mg/kg) all mice, one female rat and one male rat died. Rats orally treated with mangiferin (250-1000 mg/kg) for 28 days did not show any abnormal clinical signs or hematology alterations, when compared to control group animals. Histopathological alterations like vacuolar degeneration, necrosis and increment of apoptosis of the acinar cells were observed in the exocrine pancreas of rats at 1000 mg/kg. This suggesting that exocrine pancreas was the target organ for mangiferin’s toxicity. Conclusions: These studies indicated that acute and subchronic toxicities of mangiferin for oral exposure are low.

Context: The aqueous extract of Mangifera indica L. stem bark (MSBE) shows antioxidant, anti-inflammatory and analgesic properties. Aims: To test the MSBE in chronic constriction injury (CCI) of the sciatic nerve in rats, a classical model of neuropathic pain. Methods: Given the possibility that some clinical effect of MSBE can appear only after its chronic administration, we designed a long term medication protocol with 500 mg/kg, p.o. or distilled water daily during 8 days from 9 days post-CCI. Pregabalin (10 mg/kg, p.o.) was used as reference drug. Sham CCI animals received vehicle. Behavioral tests were carried out before CCI, at 9 and 16 days after injury. A section of sciatic nerve, 5 mm distal to the ligature site was dissected for histopathological studies. A single oral similar dose or vehicle was administered to mononeuropathic rats, 14 days after surgery. Mechano-hyperalgesia and thermal hyperalgesia of the ipsilateral paw were determined using a modification of pin prick method and the unilateral hot plate, respectively before CCI, 0, 30, 60, 120 and 180 min post-administration. Results: Repeated oral MSBE doses reduced nociceptive score, increased paw withdrawal latency and attenuated CCI-induced Wallerian degeneration-related changes involved in the hyperalgesic state of CCI rats. Likewise, MSBE shows significant mechanical and thermal anti-hyperalgesic effect from 1h after its single administration. Conclusions: The study of MSBE should be focused in neuropathic pain models since this natural product could have a clinical relevance in the treatment of neuropathic pain syndromes.

Se estudió el efecto del ozono por vía rectal a diferentes dosis sobre variables de función renal y la presión arterial sistólica en un modelo de glomerulonefritis tóxica experimental por adriamicina. La glomerulonefritis experimental es causa de insuficiencia renal, caracterizada por un daño renal progresivo. Existen diferentes esquemas de tratamiento, los cuales son muy caros y producen inmunosupresión, que afecta la calidad de vida del paciente. Para desarrollar este trabajo se utilizaron 40 ratas hembras Wistar de 200 g de peso, divididas en 4 grupos, uno control, otro control positivo, que recibieron adriamicina durante un período de 10 semanas, y otros 2 que recibieron terapia con ozono. A todos se les determinó la proteinuria, presión arterial sistólica y diuresis de 24 h. Los resultados mostraron que la terapia con ozono a una dosis de 0,3 mg/kg tuvo efecto renoprotectorThe effect of ozone by rectal route at different doses on variables of renal function and systolic arterial pressure was studied in a model of experimental toxic glomerulonephritis due to adriamicine. Experimental glomerulonephritis causes renal failure and it is characterized by a progressive renal damage. There are different treatment schemes that are very expensive and produce immunosupression, affecting the patient’s quality of life. To develop this work, 40 Wistar rats of 200 g of weight were used. They were dividided into 4 groups: a control group and a positive control group that were administered adriamicine during 10 weeks, and other 2 that received ozone therapy. Proteinuria, systolic arterial pressure and 24-hour diuresis were determined in all of them. The results showed that ozone therapy at a dosis of 0.3 mg/kg had a renal protective effect

Se evaluó la efectividad del método Túnel y se comparó con la técnica convencional de hematoxilina-eosina. Se estudió por ambas técnicas la histopatología de un carcinoma epidermoide y se observó que el método Túnel redujo los índices de apoptosisThe effectiviness of the TUNEL method was evaluated and compared with that of the conventional hematoxylineosin technique. The histopathology of a squamous cell carcinoma was studied by using both techniques and it was observed that the TUNEL method reduced the apoptosis indices

Haemophilus influenzae type b (Hib) is a Gram-negative bacterium causing diseases such as meningitis, pneumonia, epiglottis, cellulitis, septicemia and arthritis, among others. Hib-caused meningitis / Hib meningitis is a very serious disease with a death rate of more than 50 % throughout the world; therefore obtaining a vaccine against this bacterium is a goal of the highest priority. The present report presents the results of preclinical safety testing of the Quimi-Hib(r) vaccine (synthetic Hib antigen conjugated to tetanus toxoid) adjuvanted with aluminum phosphate. The battery of toxicological tests included acute toxicity (15 days), local tolerance (15 days) and repeated-dose toxicity (30 days), all of them evaluating the therapeutic dose of the vaccine as part of the studied experimental treatments. Three vaccine dose levels and a placebo (excipients plus adjuvant) were examined, administering the vaccine intramuscularly to Sprague Dawley rats of both sexes. After examining the data obtained from the administration of this wide range of doses to Sprague Dawley rats, it was concluded that the synthetic conjugate vaccine Quimi-Hib(r) adjuvanted in aluminum phosphate is not toxic and does not cause systemic adverse effects. No macroscopic alterations were observed in the studied organs, and the evaluation of the inoculation site only detected indurations caused by macrophage granulomas, resulting from the mechanism of action of the adjuvant included in the formulation.