Antiulcer Activity of Salvadora persica on Experimental ASA-Induced Ulcer in Rats: Ultrastructural Modifications

The lyophilized decoction of Salvadora persica L. roots possesses a significant protective effect on ulceration induced by ethanol, indomethacin and cold restraint stress in rats. In this work, we study the effect of chronic intragastric administration of S. persica decoction on experimental acetylsalicylic acid (ASA)-induced ulcer in rats. The ulcer index significantly decreased (U.I. 0.9 ± 1.6; P < 0.05) after treatment with a lyophilized decoction of S. persica (500 mg/kg, os), once daily for seven days, with respect to controls (U.I. 11.4 ± 2.3). The modification of gastric mucosa was observed by transmission electronic microscopy (TEM) confirming this result. In fact, in treated rats, the mucosa recovered to normal distribution. After S. persica treatment, some changes were detected in profiles of various cytoplasm organelles of parietal cells. Particularly, the intracellular canaliculi show an enlarged lumen with an increase in the number and length of microvilli. These morphological features of ..

Avaliação do efeito do eucaliptol nas convulsões induzidas por pentilenotetrazol em camundongos

The developmental process of epilepsies involves diverse mechanisms that culminate in the hyperactivity of a population of neurons, resulting in a pattern of repeated and rhythmic depolarizations. Antiepileptic drugs act by increasing GABAergic neurotransmission, reducing the effects of glutamate, or blocking ion channels, and are endowed with serious adverse effects that make it difficult for patients to adhere to treatment. This fact has encouraged the search for compounds of natural origin with potential anticonvulsant effect. Thus, the present study aimed to evaluate the effect of eucalyptol in seizures induced by pentylenetetrazole (PTZ). For this, male Swiss mice, orally treated with monotrepene, were used. The first protocol evaluated the toxicity and the estimated LD50 of the compound. Based on the value of LD50, the doses of terpene used in the behavioral and neurochemical tests were selected. For the behavioral tests, groups of mice were pretreated with saline (10 mL/kg, vol), diazepam (2 mg/kg, ip) and eucalyptol (100, 200 and 400 mg/kg, vol) and then with pentylenetetrazole 80 mg/kg, ip) and evaluated for the following parameters: seizure intensity, latency for first seizure and time of death. For neurochemical tests, groups of mice were pretreated with saline (10 mL/kg, v.o.) and eucalyptol (400 mg/kg, i.p.) and subsequently with pentylenetetrazole (80 mg/kg, i.p.); The determination of the concentration of neurotransmitters (monoamines - dopamine, noradrenaline and serotonin) and oxidative stress markers (nitrite and thiobarbituric acid reactive substances - TBARs) were the parameters evaluated. The results were analyzed by ANOVA or Kruskal-Wallis, followed by Student-Newman-Keuls, and Dunns, respectively. Values of p <0.05 were considered significant. The results showed that oral administration of eucalyptol had low toxicity and the estimated LD50 was greater than 2000 mg / kg. In the PTZ-induced seizure test, only the higher dose of monoterpene (400 mg/kg) significantly reduced seizure intensity by 60%, increased latency for onset of the first seizure by 85% and time of death of the animals in 75% in relation to the control. Similarly, treatment with eucalyptol (400 mg/kg) significantly reduced the concentration of noradrenaline, dopamine and serotonin by 50%, 33% and 70%, respectively, in relation to the PTZ-treated group (80 mg/kg). In addition, treatment with eucalyptol (400 mg/kg) significantly reduced the concentration of TBARs by 33%, but not nitrite, relative to the PTZ treated group (80 mg/kg). Taken together, the results show that the monoterpene studied has low oral toxicity and an important anticonvulsant effect, since its administration is capable of attenuating the convulsions chemically induced by pentylenetetrazol with consequent reduction of the concentration of monoamines and the reactive substances of thiobarbituric acid, elements whose increase is associated with the epileptogenesis phenomenon.O processo de desenvolvimento das epilepsias envolve mecanismos diversos que culminam na hiperatividade de uma população de neurônios, resultando em um padrão de despolarizações repetidas e rítmicas. Os fármacos antiepilépticos agem através do aumento da neurotransmissão GABAérgica, da redução dos efeitos do glutamato, ou do bloqueio de canais iônicos, sendo dotados de efeitos adversos sérios que dificultam a adesão do paciente ao tratamento. Este fato tem incentivado a busca por compostos de origem natural com potencial efeito anticonvulsivante. Desta forma, o presente trabalho teve como objetivo avaliar o efeito do eucaliptol nas convulsões induzidas por pentilenotetrazol (PTZ). Para tanto, foram utilizados camundongos Swiss machos, tratados oralmente com o monotrepeno. O primeiro protocolo realizado avaliou a toxicidade e a DL50 estimada do composto. Com base no valor da DL50, foram selecionadas as doses do terpeno utilizadas nos testes comportamentais e neuroqímicos. Para os testes comportamentais, grupos de camundongos foram previamente tratados com salina (10 mL/kg, v.o.), diazepam (2 mg/kg, i.p.) e eucaliptol (100, 200 e 400 mg/kg, v.o.) e posteriormente com pentilenotetrazol (80 mg/kg, i.p.) e avaliados quanto aos seguintes parâmetros: intensidade das convulsões, latência para primeira convulsão e tempo de morte. Para os testes neuroquímicos, grupos de camundongos foram previamente tratados com salina (10 mL/kg, v.o.) e eucaliptol (400 mg/kg, i.p.) e posteriormente com pentilenotetrazol (80 mg/kg, i.p.); a determinação da concentração de neurotransmissores (monoaminas – dopamina, noradrenalina e serotonina) e dos marcadores de estresse oxidativo (nitrito e substâncias reativas do ácido tiobarbitúrico – TBARs) foram os parâmetros avaliados. Os resultados foram analisados por ANOVA ou Kruskal-Wallis, seguido dos testes de Student-Newman-Keuls, e Dunns, respectivamente. Foram considerados significativos os valores de p < 0,05. Os resultados mostraram que a administração oral do eucaliptol apresentou baixa toxicidade e a DL50 estimada foi superior a 2000 mg/kg. No teste das convulsões induzidas por PTZ apenas a dose maior do monoterpeno (400 mg/kg) reduziu de forma significativa a intensidade das convulsões em 60%, aumentou a latência para aparecimento da primeira convulsão em 85% e o tempo de morte dos animais em 75% em relação ao controle. De forma semelhante, o tratamento com eucaliptol (400 mg/kg) reduziu de forma significativa a concentração de noradrenalina, dopamina e serotonina, em 50%, 33% e 70%, respectivamente, em relação ao grupo tratado com PTZ (80 mg/kg). Além disso, o tratamento com eucaliptol (400 mg/kg) reduziu de forma significativa a concentração de TBARs em 33%, mas não de nitrito, em relação ao grupo tratado com PTZ (80 mg/kg). Tomados em conjunto, os resultados mostram que o monoterpeno estudado apresenta baixa toxicidade oral e importante efeito anticonvulsivante, visto que sua administração é capaz de atenuar as convulsões quimicamente induzidas por pentilenotetrazol com consequente redução da concentração de monoaminas e das substâncias reativas do ácido tiobarbitúrico, elementos cujo aumento está associado ao fenômeno da epileptogênese

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Endogenous reverse transcriptase as a mediator of ursolic acid's antiproliferative and differentiating effects in human cancer cell lines

Ursolic acid (UA) is a pentacyclic triterpenoid compound that is widely distributed in the plant kingdom and has a broad range of biological effects. Here, we examined the effects of UA on the proliferation and differentiation of human tumor cell lines from melanoma (A375), glioblastoma (U87) and thyroid anaplastic carcinoma (ARO), and on the proliferation of a non-transformed human fibroblast cell line (WI-38). The results show that UA inhibits tumor cell proliferation in a dose- and time-dependent manner. Consistent with this finding, UA treatment promotes differentiation of all of the analyzed tumor cell lines. Interestingly, we found that UA inhibits the endogenous reverse transcriptase (RT) activity in tumor cells, which has recently been shown to be involved in the control of proliferation and differentiation of neoplastic cells. Considering these findings, we suggest that the observed anti-proliferative and differentiating effects of UA may be related to this target

Comparative evaluation of subtyping tools for surveillance of newly emerging HIV-1 strains

HIV-1 non-B subtypes/circulating recombinant forms (CRFs) are increasing worldwide. Since subtype identification can be clinically relevant, we assessed the added value in HIV-1 subtyping using updated molecular phylogeny (Mphy) and the performance of routinely used automated tools. Updated Mphy (2015 updated reference sequences), used as a gold standard, was performed to subtype 13,116 HIV-1 protease/reverse transcriptase sequences and then compared with previous Mphy (reference sequences until 2014) and with COMET, REGA, SCUEAL, and Stanford subtyping tools. Updated Mphy classified subtype B as the most prevalent (73.4%), followed by CRF02-AG (7.9%), C (4.6%), F1 (3.4%), A1 (2.2%), G (1.6%), CRF12-BF (1.2%), and other subtypes (5.7%). A 2.3% proportion of sequences were reassigned as different subtypes or CRFs because of misclassification by previous Mphy. Overall, the tool most concordant with updated Mphy was Stanford-v8.1 (95.4%), followed by COMET (93.8%), REGA-v3 (92.5%), Stanford-old (91.1%), and SCUEAL (85.9%). All the tools had a high sensitivity (\ue2\u89\ua598.0%) and specificity (\ue2\u89\ua595.7%) for subtype B. Regarding non-B subtypes, Stanford-v8.1 was the best tool for C, D, and F subtypes and for CRFs 01, 02, 06, 11, and 36 (sensitivity, \ue2\u89\ua592.6%; specificity, \ue2\u89\ua599.1%). A1 and G subtypes were better classified by COMET (92.3%) and REGA-v3 (98.6%), respectively. Our findings confirm Mphy as the gold standard for accurate HIV-1 subtyping, although Stanford-v8.1, occasionally combined with COMET or REGA-v3, represents an effective subtyping approach in clinical settings. Periodic updating of HIV-1 reference sequences is fundamental to improving subtype characterization in the context of an effective epidemiological surveillance of non-B strains