RESUMO
Inflammaging is a low-grade inflammatory state generated by the aging process that can contribute to frailty and age-related diseases in the elderly. However, it can have distinct effects in the elderly living in endemic areas for infectious diseases. An increased inflammatory response may confer protection against infectious agents in these areas, although this advantage can cause accelerating epigenetic aging. In this study, we evaluated the inflammatory profile and the epigenetic age of infected and noninfected individuals from an endemic area in Brazil. The profile of cytokines, chemokines and growth factors analyzed in the sera of the two groups of individuals showed similarities, although infected individuals had a higher concentration of these mediators. A significant increase in IL-1ra, CXCL8, CCL2, CCL3 and CCL4 production was associated with leprosy infection. Notably, elderly individuals displayed distinct immune responses associated with their infection status when compared to adults suggesting an adaptive remodelling of their immune responses. Epigenetic analysis also showed that there was no difference in epigenetic age between the two groups of individuals. However, individuals from the endemic area had a significant accelerated aging when compared to individuals from São Paulo, a non-endemic area in Brazil. Moreover, the latter cohort was also epigenetically aged in relation to an Italian cohort. Our data shows that living in endemic areas for chronic infectious diseases results in remodelling of inflammaging and acceleration of epigenetic aging in individuals regardless of their infectious status. It also highlights that geographical, genetic and environmental factors influence aging and immunosenescence in their pace and profile.
Assuntos
Doenças Transmissíveis , Proteína Antagonista do Receptor de Interleucina 1 , Idoso , Envelhecimento/genética , Brasil/epidemiologia , Quimiocinas , Citocinas , Epigênese Genética , HumanosRESUMO
A utilização de protocolos de sedação como auxílio na contenção de felinos para realização de coletas de sangue é de grande importância, porém a utilização de alguns fármacos pode alterar resultados e a interpretação deles. Por outro lado, a contenção física pode gerar intenso estresse, especialmente em felinos, o que também pode interferir nos resultados. Este estudo teve como objetivo avaliar exames de bioquímica clínica sob o uso de contenção física e química em gatos submetidos a dois protocolos de sedação. Foram utilizados 50 gatos, 26 fêmeas e 24 machos, sem raça definida, submetidos a contenção física e, imediatamente após, a dois protocolos de sedação, DB (dexmedetomidina 5µg/kg e butorfanol 0,3mg/kg) e DBC (dexmedetomidina 5µg/kg, butorfanol 0,3mg/kg e cetamina 3mg/kg), aplicados por via intramuscular. Amostras de sangue foram coletadas após a contenção física e, em seguida, após o uso de um dos protocolos de sedação. Foram avaliados: ureia, creatinina, alaninoaminotransferase (ALT), fosfatase alcalina, proteína sérica total (PST), albumina, globulinas, colesterol, triglicérides, cálcio, magnésio e cloretos de amostras de soro, lactato e glicose de amostras de plasma fluoretado. Foi encontrada diferença estatística entre grupos para albumina, triglicérides, PST e colesterol, com maiores valores sendo encontrados no grupo DBC. Entre momentos, houve diferença para colesterol e fosfatase alcalina, com maiores valores no momento contenção física somente no grupo DBC. Já a glicose teve maiores valores após a sedação em ambos os grupos. O estudo revelou que o uso destes protocolos implica restrições para alguns parâmetros bioquímicos aqui estudados e que suas interpretações devem ser avaliadas cuidadosamente.(AU)
The use of sedation protocols to assist in the restraint of cats to perform blood collections is of great importance, but the use of some drugs can alter the results and interpretation. Moreover, the physical restraint may generate intense stress, especially in animals of the feline species, which may also interfere with the results. This study aimed to evaluate examinations of clinical biochemistry in the use of physical restraint and chemistry in cats subjected to two sedation protocols. We used 50 cats, 26 females and 24 males, of mixed-breed, who underwent physical restraint and immediately after underwent two sedation protocols, DB (dexmedetomidine 5µg / kg and 0.3mg butorphanol / kg) and DBC (dexmedetomidine 5µg / kg butorphanol 0.3mg / kg ketamine and 3mg / kg), applied intramuscularly. Blood samples were taken after physical restraint and then after the use of one of the sedation protocols. The following parameters were evaluated: urea, creatinine, alanine aminotransferase (ALT), alkaline phosphatase (ALP), total serum protein (TP), albumin, globulin, cholesterol, triglycerides, calcium, magnesium and chloride in serum samples, and lactate and glucose in fluoride plasma samples. Statistical difference was found between groups for albumin, triglycerides, TP and cholesterol with higher values being found in the DBC group. A statistical difference between moments was found for cholesterol, and ALP with higher values in physical restraint only in the DBC group. Glucose had greater values after sedation for both groups. The study revealed that the use of these protocols implies restrictions on some biochemical parameters studied here, and that their interpretations should be evaluated carefully.(AU)
Assuntos
Animais , Gatos , Analgesia/métodos , Anestesia/veterinária , Butorfanol/administração & dosagem , Dexmedetomidina/administração & dosagem , Ketamina/administração & dosagem , Glucose/análise , Testes Hematológicos/veterináriaRESUMO
A utilização de protocolos de sedação como auxílio na contenção de felinos para realização de coletas de sangue é de grande importância, porém a utilização de alguns fármacos pode alterar resultados e a interpretação deles. Por outro lado, a contenção física pode gerar intenso estresse, especialmente em felinos, o que também pode interferir nos resultados. Este estudo teve como objetivo avaliar exames de bioquímica clínica sob o uso de contenção física e química em gatos submetidos a dois protocolos de sedação. Foram utilizados 50 gatos, 26 fêmeas e 24 machos, sem raça definida, submetidos a contenção física e, imediatamente após, a dois protocolos de sedação, DB (dexmedetomidina 5µg/kg e butorfanol 0,3mg/kg) e DBC (dexmedetomidina 5µg/kg, butorfanol 0,3mg/kg e cetamina 3mg/kg), aplicados por via intramuscular. Amostras de sangue foram coletadas após a contenção física e, em seguida, após o uso de um dos protocolos de sedação. Foram avaliados: ureia, creatinina, alaninoaminotransferase (ALT), fosfatase alcalina, proteína sérica total (PST), albumina, globulinas, colesterol, triglicérides, cálcio, magnésio e cloretos de amostras de soro, lactato e glicose de amostras de plasma fluoretado. Foi encontrada diferença estatística entre grupos para albumina, triglicérides, PST e colesterol, com maiores valores sendo encontrados no grupo DBC. Entre momentos, houve diferença para colesterol e fosfatase alcalina, com maiores valores no momento contenção física somente no grupo DBC. Já a glicose teve maiores valores após a sedação em ambos os grupos. O estudo revelou que o uso destes protocolos implica restrições para alguns parâmetros bioquímicos aqui estudados e que suas interpretações devem ser avaliadas cuidadosamente.(AU)
The use of sedation protocols to assist in the restraint of cats to perform blood collections is of great importance, but the use of some drugs can alter the results and interpretation. Moreover, the physical restraint may generate intense stress, especially in animals of the feline species, which may also interfere with the results. This study aimed to evaluate examinations of clinical biochemistry in the use of physical restraint and chemistry in cats subjected to two sedation protocols. We used 50 cats, 26 females and 24 males, of mixed-breed, who underwent physical restraint and immediately after underwent two sedation protocols, DB (dexmedetomidine 5µg / kg and 0.3mg butorphanol / kg) and DBC (dexmedetomidine 5µg / kg butorphanol 0.3mg / kg ketamine and 3mg / kg), applied intramuscularly. Blood samples were taken after physical restraint and then after the use of one of the sedation protocols. The following parameters were evaluated: urea, creatinine, alanine aminotransferase (ALT), alkaline phosphatase (ALP), total serum protein (TP), albumin, globulin, cholesterol, triglycerides, calcium, magnesium and chloride in serum samples, and lactate and glucose in fluoride plasma samples. Statistical difference was found between groups for albumin, triglycerides, TP and cholesterol with higher values being found in the DBC group. A statistical difference between moments was found for cholesterol, and ALP with higher values in physical restraint only in the DBC group. Glucose had greater values after sedation for both groups. The study revealed that the use of these protocols implies restrictions on some biochemical parameters studied here, and that their interpretations should be evaluated carefully.(AU)
Assuntos
Animais , Gatos , Dexmedetomidina/administração & dosagem , Butorfanol/administração & dosagem , Ketamina/administração & dosagem , Anestesia/veterinária , Analgesia/métodos , Testes Hematológicos/veterinária , Glucose/análiseRESUMO
BACKGROUND AND PURPOSE: Many in vitro and fewer in vivo studies have shown that tetracyclines present anti-inflammatory activity. We investigated if a novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline, 12S-hydroxy-1,12-pyrazolinominocycline (PMIN), also induced antinociceptive and anti-inflammatory effects. EXPERIMENTAL APPROACH: Antibacterial effects against a minocycline-sensitive Staphylococcus aureus strain were evaluated by applying a cylinder-plate agar diffusion technique. Antibacterial effects of diluted serum from mice pre-treated with minocycline or PMIN were also evaluated. Ca2+ binding activity was assessed by spectrophotometry. Formalin-induced nociceptive responses and carrageenan-induced paw oedema were evaluated in mice. The rota-rod apparatus was used to evaluate motor coordination. KEY RESULTS: Minocycline, but not PMIN, inhibited bacterial growth. Serum from mice treated with minocycline, but not with PMIN, also induced such an effect. The UV absorption spectrum of solutions of minocycline, but not those of PMIN, was markedly changed in the presence of Ca2+. Minocycline or PMIN inhibited both phases of formalin-induced nociception and carrageenan-induced paw oedema. It is unlikely that antinociception resulted from lack of motor coordination, as tetracycline did not impair the performance of mice on the rotating rod. CONCLUSIONS AND IMPLICATIONS: These results indicate that inhibition of nociception and oedema by tetracyclines is neither necessarily linked to antibacterial nor to Ca2+ chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the treatment of painful and inflammatory diseases, as its lack of antibacterial and Ca2+ chelating activities might confer greater safety over conventional tetracyclines.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Edema/tratamento farmacológico , Minociclina/uso terapêutico , Dor/tratamento farmacológico , Pirazóis/uso terapêutico , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Cálcio/metabolismo , Cátions Bivalentes/metabolismo , Quelantes/química , Quelantes/farmacologia , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Minociclina/química , Minociclina/farmacologia , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Medição da Dor , Pirazóis/química , Pirazóis/farmacologia , Teste de Desempenho do Rota-Rod , Staphylococcus aureus/efeitos dos fármacosRESUMO
We investigated the anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex (5.5 or 11 mg/kg) in male Wistar rats (180-300 g, N = 6) and compared it to free diclofenac (5 or 10 mg/kg) and to the combination of diclofenac (5 or 10 mg/kg) and zinc acetate (1.68 or 3.5 mg/kg). The carrageenin-induced paw edema and the cotton pellet-induced granulomatous tissue formation models were used to assess the anti-inflammatory activity, and the Hargreaves model of thermal hyperalgesia was used to assess the antinociceptive activity. To investigate the effect of orally or intraperitoneally (ip) administered drugs on cold-induced gastric lesions, single doses were administered before exposing the animals to a freezer (-18ºC) for 45 min in individual cages. We also evaluated the gastric lesions induced by multiple doses of the drugs. Diclofenac plus zinc complex had the same anti-inflammatory and antinociceptive effects as diclofenac alone. Gastric lesions induced by a single dose administered per os and ip were reduced in the group treated with zinc-diclofenac when compared to the groups treated with free diclofenac or diclofenac plus zinc acetate. In the multiple dose treatment, the complex induced a lower number of the most severe lesions when compared to free diclofenac and diclofenac plus zinc acetate. In conclusion, the present study demonstrates that the zinc-diclofenac complex may represent an important therapeutic alternative for the treatment of rheumatic and inflammatory conditions, as its use may be associated with a reduced incidence of gastric lesions.
Assuntos
Animais , Masculino , Ratos , Analgésicos , Anti-Inflamatórios , Diclofenaco , Úlcera Gástrica , Acetato de Zinco , Carragenina , Combinação de Medicamentos , Edema , Granuloma , Hiperalgesia , Ratos WistarRESUMO
We investigated the anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex (5.5 or 11 mg/kg) in male Wistar rats (180-300 g, N = 6) and compared it to free diclofenac (5 or 10 mg/kg) and to the combination of diclofenac (5 or 10 mg/kg) and zinc acetate (1.68 or 3.5 mg/kg). The carrageenin-induced paw edema and the cotton pellet-induced granulomatous tissue formation models were used to assess the anti-inflammatory activity, and the Hargreaves model of thermal hyperalgesia was used to assess the antinociceptive activity. To investigate the effect of orally or intraperitoneally (ip) administered drugs on cold-induced gastric lesions, single doses were administered before exposing the animals to a freezer (-18 degrees C) for 45 min in individual cages. We also evaluated the gastric lesions induced by multiple doses of the drugs. Diclofenac plus zinc complex had the same anti-inflammatory and antinociceptive effects as diclofenac alone. Gastric lesions induced by a single dose administered per os and ip were reduced in the group treated with zinc-diclofenac when compared to the groups treated with free diclofenac or diclofenac plus zinc acetate. In the multiple dose treatment, the complex induced a lower number of the most severe lesions when compared to free diclofenac and diclofenac plus zinc acetate. In conclusion, the present study demonstrates that the zinc-diclofenac complex may represent an important therapeutic alternative for the treatment of rheumatic and inflammatory conditions, as its use may be associated with a reduced incidence of gastric lesions.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Diclofenaco/farmacologia , Úlcera Gástrica/tratamento farmacológico , Acetato de Zinco/farmacologia , Animais , Carragenina , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Edema/tratamento farmacológico , Granuloma/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Masculino , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamenteRESUMO
We have investigated the hypoglycemic effect induced by the starch obtained from the unripe fruits of Solanum lycocarpum (Solanaceae). Per os administration of the starch (1000 or 2000 mg/kg, twice daily for 7 days, N = 6) did not change glycemia levels of nondiabetic female Swiss mice weighing 25-30 g. In streptozotocin-induced diabetic mice, similar treatment with the starch did not change the elevated glycemia 3 h after the last dose (diabetic treated with saline = 288 17/309 18; starch 1000 mg/kg = 295 +/- 33; starch 2000 mg/kg = 258 +/- 37; N = 5). In animals fasted for 15 h, per os administration of glucose (600 mg/kg) significantly increased glycemia 1 h later. Previous (-30 min) treatment of the animals with the starch (1000 or 2000 mg/kg; N = 5) did not change the increase of glycemia. Per os administration of the starch (1000 or 2000 mg kg-1 day-1, twice daily for 7 days) did not induce body weight gain or loss. The chemical analysis of the starch indicated the presence of glycoalkaloids, a finding that represents a reason for concern since many of these substances are generally toxic. In interviews with 56 diabetic patients, 29 medicinal plants were reported as useful in their treatment of diabetes and S. lycocarpum was the sixth most frequently mentioned. All patients interviewed reported that they also used insulin or oral hypoglycemic drugs. The results of the present study do not provide evidence for a hypoglycemic effect associated with the polysaccharide fraction of S. lycocarpum in either normal or hyperglycemic mice. These data demonstrate the need for adequate pharmacological investigation of the natural products widely used in folk medicine.
Assuntos
Índice Glicêmico/efeitos dos fármacos , Solanum/química , Amido/farmacologia , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Masculino , Camundongos , Extratos Vegetais/farmacologia , Amido/químicaRESUMO
We have investigated the hypoglycemic effect induced by the starch obtained from the unripe fruits of Solanum lycocarpum (Solanaceae). Per os administration of the starch (1000 or 2000 mg/kg, twice daily for 7 days, N = 6) did not change glycemia levels of nondiabetic female Swiss mice weighing 25-30 g. In streptozotocin-induced diabetic mice, similar treatment with the starch did not change the elevated glycemia 3 h after the last dose (diabetic treated with saline = 288 ± 17/309 ± 18; starch 1000 mg/kg = 295 ± 33; starch 2000 mg/kg = 258 ± 37; N = 5). In animals fasted for 15 h, per os administration of glucose (600 mg/kg) significantly increased glycemia 1 h later. Previous (-30 min) treatment of the animals with the starch (1000 or 2000 mg/kg; N = 5) did not change the increase of glycemia. Per os administration of the starch (1000 or 2000 mg kg-1 day-1, twice daily for 7 days) did not induce body weight gain or loss. The chemical analysis of the starch indicated the presence of glycoalkaloids, a finding that represents a reason for concern since many of these substances are generally toxic. In interviews with 56 diabetic patients, 29 medicinal plants were reported as useful in their treatment of diabetes and S. lycocarpum was the sixth most frequently mentioned. All patients interviewed reported that they also used insulin or oral hypoglycemic drugs. The results of the present study do not provide evidence for a hypoglycemic effect associated with the polysaccharide fraction of S. lycocarpum in either normal or hyperglycemic mice. These data demonstrate the need for adequate pharmacological investigation of the natural products widely used in folk medicine
Assuntos
Humanos , Animais , Masculino , Feminino , Camundongos , Glicemia , Solanum lycopersicum , Extratos Vegetais , Amido , Diabetes Mellitus Experimental , Plantas Medicinais , Amido , Inquéritos e QuestionáriosRESUMO
The effect of some B vitamins in chemical and thermal models of nociception in mice was investigated. The association thiamine/pyridoxine/cyanocobalamin (TPC, 20-200 mg/kg, i.p. or per os), thiamine, pyridoxine (50-200 mg/kg, i.p.) or riboflavin (3-100 mg/kg, i.p) induced an antinociceptive effect, not changed by naloxone (10 mg/kg, i.p.), in the acetic acid writhing model. Treatment for 7 days with thiamine/pyridoxine/cyanocobalamin (100 or 200 mg/kg, i.p.), thiamine (50 or 100 mg/kg) or pyridoxine (50 or 100 mg/kg) or acute treatment with riboflavin (6 or 12 mg/kg, i.p) inhibited the nociceptive response induced by formaldehyde. The B vitamins did not inhibit the nociceptive response in the hot-plate model. Both 7-day thiamine/pyridoxine/cyanocobalamin (100 mg/kg, i.p.) or acute riboflavin (25 or 50 mg/kg, i.p.) treatment partially reduced formaldehyde-induced hindpaw oedema. The B vitamins antinociceptive effect may involve inhibition of the synthesis and/or action of inflammatory mediators since it was not observed in the hot-plate model, was not reversed by naloxone, only the second phase of the formaldehyde-induced nociceptive response was inhibited, and formaldehyde-induced hindpaw oedema was reduced.
Assuntos
Nociceptores/efeitos dos fármacos , Dor/prevenção & controle , Complexo Vitamínico B/farmacologia , Ácido Acético , Animais , Constrição , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/prevenção & controle , Formaldeído , Membro Posterior , Injeções Intraperitoneais , Injeções Subcutâneas , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Naloxona/farmacologia , Dor/induzido quimicamente , Dor/fisiopatologia , Medição da Dor/métodos , Piridoxina/farmacologia , Riboflavina/farmacologia , Tiamina/farmacologia , Vitamina B 12/farmacologiaRESUMO
We have demonstrated that the hepatic function may have an important role in the development of tolerance to the pyrogenic effect induced by endotoxin. To further investigate if the role of the hepatic function in the development of tolerance also extends to that induced by other pyrogenic stimuli, we investigated the effect of galactosamine, a specific inhibitor of the hepatic protein synthesis, on the development of tolerance to the pyrogenic effect induced by muramyl dipeptide (MDP) in rats. Pyrogenic tolerance was observed after the second intravenous or intraperitoneal injection of MDP (500 microgram/kg), 24 h after the first injection, similar to what was observed with endotoxin. Pyrogenic tolerance was abolished when galactosamine (300 mg/kg ip) was injected simultaneously with MDP (500 microgram/kg iv) on the first day. When uridine (600 mg/kg ip) was administered simultaneously with galactosamine (300 mg/kg ip) and the first injection of MDP (500 microgram/kg ip), pyrogenic tolerance was again observed after the second injection of the peptidoglycan. In conclusion, the hepatic function may not be important only for the development of tolerance to endotoxin, but also to a totally different pyrogenic stimulus such as MDP.