Ayahuasca and its major component harmine promote antinociceptive effects in mouse models of acute and chronic pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayahuasca (AYA) is a psychedelic brew used in religious ceremonies. It is broadly used as a sacred medicine for treating several ailments, including pain of various origins. AIM OF THE STUDY: To investigate the antinociceptive effects of AYA and its mechanisms in preclinical models of acute and chronic pain in mice, in particular during experimental neuropathy. MATERIALS AND METHODS: The antinociceptive effects of AYA administered orally were assessed in the following models of pain: formalin test, Complete Freund's Adjuvant (CFA)-induced inflammation, tail flick test, and partial sciatic nerve ligation model of neuropathic pain. Antagonism assays and Fos immunohistochemistry in the brain were performed. AYA-induced toxicity was investigated. AYA was chemically characterized. The antinociceptive effect of harmine, the major component present in AYA, was investigated. RESULTS: AYA (24-3000 µL/kg) dose-dependently reduced formalin-induced pain-like behaviors and CFA-induced mechanical allodynia but did not affect CFA-induced paw edema or tail flick latency. During experimental neuropathy, single treatments with AYA (24-3000 µL/kg) reduced mechanical allodynia; daily treatments once or twice a day for 14 days promoted consistent and sustained antinociception. The antinociceptive effect of AYA (600 µL/kg) was reverted by bicuculline (1 mg/kg) and methysergide (5 mg/kg), but not by naloxone (5 mg/kg), phaclofen (2 mg/kg), and rimonabant (10 mg/kg), suggesting the roles of GABAA and serotonergic receptors. AYA increased Fos expression in the ventrolateral periaqueductal gray and nucleus raphe magnus after 1 h, but not after 6 h or 14 days of daily treatments. AYA (600 µL/kg) twice a day for 14 days did not alter mice's motor function, spontaneous locomotion, body weight, food and water intake, hematological, biochemical, and histopathological parameters. Harmine (3.5 mg/kg) promoted consistent antinociception during experimental neuropathy. CONCLUSIONS: AYA promotes consistent antinociceptive effects in different mouse models of pain without inducing detectable toxic effects. Harmine is at least partially accountable for the antinociceptive properties of AYA.

Effects of photobiomodulation therapy on the local experimental envenoming by Bothrops leucurus snake.

Bothrops leucurus is the major causative agent of snakebites in Brazil's Northeast. The systemic effects of its venom are effectively neutralized by antivenom therapy, preventing bitten patients' death. However, antivenom fails in neutralizing local effects that include intense pain, edema, bleeding, and myonecrosis. Such effects can lead to irreversible sequels, representing a clinically relevant issue for which there is no current effective treatment. Herein, the effects of photobiomodulation therapy (PBMT) were tested in the local actions induced by B. leucurus venom (BLV) in mice (n = 123 animals in 20 experimental groups). A continuous emission AlGaAs semiconductor diode laser was used in two wavelengths (660 or 780 nm). Mechanical nociceptive thresholds were assessed with the electronic von Frey apparatus. Local edema was determined by measuring the increase in paw thickness. Hemorrhage was quantified by digital measurement of the bleeding area. Myotoxicity was evaluated by serum creatine kinase (CK) activity and histopathological analysis. PBMT promoted anti-hypernociception in BLV-injected mice; irradiation with the 660 nm laser resulted in faster effect onset than the 780 nm laser. Both laser protocols reduced paw edema formation, whether irradiation was performed immediately or half an hour after venom injection. BLV-induced hemorrhage was not altered by PBMT. Laser irradiation delayed, but did not prevent myotoxicity caused by BLV, as shown by a late increase in CK activity and histopathological alterations. PBMT was effective in the control of some of the major local effects of BLV refractory to antivenom. It is a potential complementary therapy that could be used in bothropic envenoming, minimizing the morbidity of these snakebite accidents.

Fat embolism in liposuction and intramuscular grafts in rabbits.

PURPOSE: To evaluate the effects of fat embolism in organs such as lung and liver. METHODS: Twenty rabbits underwent autologous intramuscular fat grafting in the right thigh after liposuction. The groups were determined according to the postoperative day that occurred in euthanasia: 60, 90 and 120 day. Then, lung and liver were excised and sent to the histopathology laboratory for analysis in search of late injury secondary to a prior event of fat embolism in the tissues. RESULTS: The results showed a change in the macroscopic sample with discoloration of the liver tissue heterogeneously. There were no changes consistent with embolic effect under the microscope. CONCLUSION: The option of performing a technique of fat grafting with a less traumatic surgical procedure can be considered protective against embolic events, with no impact to late embolic events on the tissues.

Fat embolism in liposuction and intramuscular grafts in rabbits / Embolia gordurosa na lipoaspiração e enxertia intramuscular em coelhos

PURPOSE: To evaluate the effects of fat embolism in organs such as lung and liver. METHODS: Twenty rabbits underwent autologous intramuscular fat grafting in the right thigh after liposuction. The groups were determined according to the postoperative day that occurred in euthanasia: 60, 90 and 120 day. Then, lung and liver were excised and sent to the histopathology laboratory for analysis in search of late injury secondary to a prior event of fat embolism in the tissues. RESULTS: The results showed a change in the macroscopic sample with discoloration of the liver tissue heterogeneously. There were no changes consistent with embolic effect under the microscope. CONCLUSION: The option of performing a technique of fat grafting with a less traumatic surgical procedure can be considered protective against embolic events, with no impact to late embolic events on the tissues.

OBJETIVO: Avaliar a repercussão da embolia gordurosa em órgãos como pulmão e fígado. MÉTODOS: Vinte coelhos foram submetidos à enxertia autóloga intramuscular de gordura em coxa direita após lipoaspiração. Os grupos foram determinados conforme os dias pós-operatórios (DPO) em que ocorreu a eutanásia: 60 DPO, 90DPO, 120 DPO. Em seguida, o pulmão e o fígado foram ressecados e encaminhados ao laboratório de histopatologia para análise em busca de lesão tardia secundária a evento de embolia gordurosa prévia nos tecidos. RESULTADOS: Foi evidenciada uma alteração na amostra a analise macroscópica com alteração da coloração do tecido hepático de forma heterogênea. Não houve alterações compatíveis com repercussão de processo embólico à microscopia. CONCLUSÃO: A opção pela realização de uma técnica de lipoenxertia menos traumática e com pequeno tempo cirúrgico pode ser considerada protetora para eventos embólicos, não havendo repercussão embólica a tardiamente.

Evaluation of the donor site after liposuction with a syringe in rabbits.

PURPOSE: To evaluate the donor site of adipocytes as well as histopathological alterations secondary to liposuction. METHODS: All animals underwent liposuction with a syringe on the right side of the back. While the left side of the back was used as control and did not undergo intervention. The 10 rabbits were divided into two groups A and B according the postoperative day which were submitted to euthanasia: 90 and 120 days. All adipose tissue from the donor site was analyzed and compared with the control macroscopic and light microscopy. Tissues were weighed and analyzed searching for histological changes and late inflammatory response to trauma such as fibrosis, fat necrosis and inflammation and macrophage infiltration. RESULTS: There was wide variation in adipose tissue volume between the experimental and the control on macroscopic analysis. The presence of histopathological changes was found in two samples at 90 days. CONCLUSIONS: There was a relationship between the presence of fibrosis with the weight and number of days after liposuction surgery in rabbits. The study show macroscopic difference between control and experiment sides in all rabbits.

Evaluation of the donor site after liposuction with a syringe in rabbits / Avaliação da zona doadora após lipoaspiração com seringa em coelhos

PURPOSE: To evaluate the donor site of adipocytes as well as histopathological alterations secondary to liposuction. METHODS: All animals underwent liposuction with a syringe on the right side of the back. While the left side of the back was used as control and did not undergo intervention. The 10 rabbits were divided into two groups A and B according the postoperative day which were submitted to euthanasia: 90 and 120 days. All adipose tissue from the donor site was analyzed and compared with the control macroscopic and light microscopy. Tissues were weighed and analyzed searching for histological changes and late inflammatory response to trauma such as fibrosis, fat necrosis and inflammation and macrophage infiltration. RESULTS: There was wide variation in adipose tissue volume between the experimental and the control on macroscopic analysis. The presence of histopathological changes was found in two samples at 90 days. CONCLUSIONS: There was a relationship between the presence of fibrosis with the weight and number of days after liposuction surgery in rabbits. The study show macroscopic difference between control and experiment sides in all rabbits.

OBJETIVO: Avaliar a zona doadora de adipócitos bem como as alterações histopatológicas secundárias a lipoaspiração. MÉTODOS: Todos os animais foram submetidos à lipoaspiração com seringa no lado direito do dorso. Enquanto o lado esquerdo do dorso foi usado como controle, não sofrendo intervenção. Os 10 coelhos foram divididos em dois grupos A e B conforme o dia pós-operatório (DPO) os quais foram submetidos à eutanásia: 90 DPO e 120 DPO. Todo tecido adiposo da zona doadora foi analisado e comparados com o controle macroscopicamente e à microscopia óptica. Os tecidos foram pesados e foram analisadas as variações histológicas em busca de uma resposta inflamatória tardia ao trauma como fibrose, inflamação, necrose gordurosa e infiltrado macrofágico. RESULTADOS: Foi observada grande variação de volume de tecido adiposo entre o experimento e o controle do dorso a macroscópica e a presença de alteração histopatológica em duas amostras aos 90 dias. CONCLUSÕES: Houve relação entre a presença de fibrose com o peso e numero de dias pós-operatório na lipoaspiração de coelhos. O estudo mostrou diferença entre os lados experimento e controle em todos os coelhos.

Post-kala-azar dermal leishmaniasis associated with AIDS.

Post-kala-azar dermal leishmaniasis (PKDL) is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area) presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

Post-kala-azar dermal leishmaniasis associated with AIDS

Post-kala-azar dermal leishmaniasis (PKDL) is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area) presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature

Post-kala-azar dermal leishmaniasis associated with AIDS

Post-kala-azar dermal leishmaniasis (PKDL) is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area) presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

Post-kala-azar dermal leishmaniasis associated with AIDS.

Post-kala-azar dermal leishmaniasis (PKDL) is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area) presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.