Search

Background and aimsCurrent treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier.MethodsFive hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32-79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion.ResultsA new criterion of evaluating UDCA responses at 1 month was established as: ALP ≤ 2.5 × upper limit of normal (ULN) and AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi'an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi'an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients' capacity of Xi'an criterion was confirmed in both early and late-stage PBC.ConclusionsXi'an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi'an criterion can facilitate early identification of patients requiring new therapeutic approaches.

Spiny lobsters (Panulirus sp.) were valuable and one of the most popular Indonesian export commodities. Some approaches were made to increase the quantity and quality of cultivated spiny lobsters. Land-based mariculture with Recirculating Aquaculture System (RAS) was applied to increase lobster harvesting and optimize environmental quality by adjusting water alkalinity. This study aimed to determine the optimum level of alkalinity for spiny lobsters Panulirus homarus rearing in RAS. This study investigated the effects of applying four water alkalinity levels (Control, 125, 200, and 275 mg L-1 CaCO3) on the biochemical responses of P. homarus observed in the hemolymph in terms of Total Hemocyte Count (THC), glucose, total protein, calcium, and pH levels. Furthermore, we also studied the alkalinity effects on lobster production performance parameters in terms of body weight gain, body length, Survival Rate (SR), Specific Growth Rate (SGR), and Feed Conversion Ratio (FCR). Lobsters with an initial weight rate of 58.05±1.69 g and an initial total length rate of 115.33±1.52 mm were reared for 60 days in a recirculation system. Results of water quality parameters such as ammonia, nitrite, nitrate, dissolved oxygen, temperature, and salinity during the study were available for lobster rearing. Different alkalinity levels affected the biochemical responses and production performance of lobsters. The best alkalinity level to reared Panulirus sp. in the recirculation system during this study was 200 mg L-1 CaCO3 so that it could achieve the highest survival rate of 86.67% with SGR 0.60±0.01 % day-1.

Late blight (LB) caused by the Phytophthora infestans is a devastating tomato disease, distributed worldwide. Tomato wild species could be a potential source of resistance, however, there are little data about their biochemical response to LB infection. Therefore the aim of the study was to evaluate total phenolic and total flavonoid content and antioxidative activity in the leaves of wild (Solanum pimpinellifolium) and cultivated genotype (Bizon) depending on disease severity. S. pimpinellifolium compared to Bizon was less susceptible and had five times lower disease severity index (11% and 55% respectively). Additionally, during the disease progression wild genotype showed a much slower decrease of total biochemical parameters compared to the cultivated one. Parameters such as total phenolic content (TP), DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging test and ABTS (2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) radical scavenging activity in the symptomless leaves and the leaves infection 10-25% remained the same in S. pimpinellifolium. The susceptible genotype Bizon had about 40% of leaves with the disease severity 25-50%, and a rapid decrease of all biochemical parameters. A strong negative correlation was observed between late blight infection and biochemical parameters in Bizon, while in S. pimpinellifolium late blight infection negatively correlated only with TP, TF (total flavonoid content) and total antioxidant activity (TAA).

CONTEXT: First-generation somatostatin receptor ligands (fg-SRLs) represent the mainstay of medical therapy for acromegaly, but they provide biochemical control of disease in only a subset of patients. Various pretreatment biomarkers might affect biochemical response to fg-SRLs. OBJECTIVE: To identify clinical predictors of the biochemical response to fg-SRLs monotherapy defined as biochemical response (insulin-like growth factor (IGF)-1 ≤ 1.3 × ULN (upper limit of normal)), partial response (>20% relative IGF-1 reduction without normalization), and nonresponse (≤20% relative IGF-1 reduction), and IGF-1 reduction. DESIGN: Retrospective multicenter study. SETTING: Eight participating European centers. METHODS: We performed a meta-analysis of participant data from 2 cohorts (Rotterdam and Liège acromegaly survey, 622 out of 3520 patients). Multivariable regression models were used to identify predictors of biochemical response to fg-SRL monotherapy. RESULTS: Lower IGF-1 concentration at baseline (odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.72-0.95 IGF-1 ULN, P = .0073) and lower bodyweight (OR = 0.99, 95% CI 0.98-0.99 kg, P = .038) were associated with biochemical response. Higher IGF-1 concentration at baseline (OR = 1.40, (1.19-1.65) IGF-1 ULN, P ≤ .0001), the presence of type 2 diabetes (oral medication OR = 2.48, (1.43-4.29), P = .0013; insulin therapy OR = 2.65, (1.02-6.70), P = .045), and higher bodyweight (OR = 1.02, (1.01-1.04) kg, P = .0023) were associated with achieving partial response. Younger patients at diagnosis are more likely to achieve nonresponse (OR = 0.96, (0.94-0.99) year, P = .0070). Baseline IGF-1 and growth hormon

Studies have shown high levels of contamination of both metals and organochlorine pesticides (OCPs) in aquatic systems of the world renowned Kruger National Park, South Africa. With effects evident in top predators, including, unexplained Crocodylus niloticus deaths and organ level and histological changes in Hydrocynus vittatus. A suite of biomarkers reflecting exposure and were selected to evaluate biological responses of H. vittatus to anthropogenic stressors as well as to evaluate whether the chosen suite of biomarkers could successfully distinguish between the different pollution profiles present in the selected rivers. During this study a clear relationship was found between exposure to environmental contaminants and the concomitant responses of H. vittatus to these stressors. The ensuing biomarker responses indicated that there is a physiological attempt to deal with, and mitigate the deleterious effects that metals and OCPs may induce. In the Luvuvhu River there is a clear indication in H. vittatus of the stimulation of anti-oxidant protective mechanisms in response to internal OCP exposure. This is reflected by the increasing cytochrome P-450, superoxide dismutase, and more specifically reduced glutathione, which resulted in decreased lipid and protein breakdown (reflected in decreased lipid peroxidation and protein carbonyl levels). Consequently H. vittatus populations of the Luvuvhu River are under greater cumulative stress and this is reflected in the lower energy budgets. Our results further show the integrated application value of the current suite of biomarkers in assessing responses of subtropical fish to metal and OCP exposure as the entire suite of biomarkers when used in conjunction were able to explain 100% of the variation in the data

Studies have shown high levels of contamination of both metals and organochlorine pesticides (OCPs) in aquatic systems of the world renowned Kruger National Park, South Africa. With effects evident in top predators, including, unexplained Crocodylus niloticus deaths and organ level and histological changes in Hydrocynus vittatus. A suite of biomarkers reflecting exposure and were selected to evaluate biological responses of H. vittatus to anthropogenic stressors as well as to evaluate whether the chosen suite of biomarkers could successfully distinguish between the different pollution profiles present in the selected rivers. During this study a clear relationship was found between exposure to environmental contaminants and the concomitant responses of H. vittatus to these stressors. The ensuing biomarker responses indicated that there is a physiological attempt to deal with, and mitigate the deleterious effects that metals and OCPs may induce. In the Luvuvhu River there is a clear indication in H. vittatus of the stimulation of anti-oxidant protective mechanisms in response to internal OCP exposure. This is reflected by the increasing cytochrome P-450, superoxide dismutase, and more specifically reduced glutathione, which resulted in decreased lipid and protein breakdown (reflected in decreased lipid peroxidation and protein carbonyl levels). Consequently H. vittatus populations of the Luvuvhu River are under greater cumulative stress and this is reflected in the lower energy budgets. Our results further show the integrated application value of the current suite of biomarkers in assessing responses of subtropical fish to metal and OCP exposure as the entire suite of biomarkers when used in conjunction were able to explain 100% of the variation in the data

Background/Purpose: Somatostatin analogues are the cornerstone of systemic therapy for metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours for both hormonal control and antiproliferative effect. Dose escalation of somatostatin analogues is often utilized in clinical practice, but small studies have yielded mixed results. The aim of this study was to systematically determine the efficacy and safety of escalated-dose somatostatin analogues in the above setting. Method(s): Eligible trials (using more than 30 mg octreotide or 120 mg lanreotide/28 days) were identified from MEDLINE, EMBASE, other databases and conference proceedings. Demographics, disease control rate, objective response rate, biochemical response, improvement in symptoms and toxicity were abstracted. Trials were synthesized qualitatively. Result(s): Eighteen studies (1002 patients) were identified. The risk of bias was moderate for objective response outcomes, but high for the outcomes of symptom control and toxicity due to open-label trial designs. Disease control rates ranged from 30 to 100%, but response rates were modest (at 0-14%). Rates of biochemical improvement (27-100%) and symptom improvement (23-100%) ranged widely depending on the population studied and the definition of response. The most common toxicities were fatigue, diarrhoea, abdominal discomfort and cholelithiasis, with no severe or unexpected toxicities compared to standard-dose somatostatin analogues. Conclusion(s): The current evidence indicates that escalated-dose somatostatin analogues are well-tolerated in patients with gastroenteropancreatic neuroendocrine tumours, with significant rates of disease control but low rates of tumour response. It was difficult to judge the exact rate of biochemical response or symptomatic improvement. There is a need for large, prospective studies investigating the role of escalated-dose somatostatin analogues in the treatment of metastatic gastroenteropancreatic neuroendoc

Background/Purpose: Somatostatin analogues are the cornerstone of systemic therapy for metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours for both hormonal control and antiproliferative effect. Dose escalation of somatostatin analogues is often utilized in clinical practice, but small studies have yielded mixed results. The aim of this study was to systematically determine the efficacy and safety of escalated-dose somatostatin analogues in the above setting. Method(s): Eligible trials (using more than 30 mg octreotide or 120 mg lanreotide/28 days) were identified from MEDLINE, EMBASE, other databases and conference proceedings. Demographics, disease control rate, objective response rate, biochemical response, improvement in symptoms and toxicity were abstracted. Trials were synthesized qualitatively. Result(s): Eighteen studies (1002 patients) were identified. The risk of bias was moderate for objective response outcomes, but high for the outcomes of symptom control and toxicity due to open-label trial designs. Disease control rates ranged from 30 to 100%, but response rates were modest (at 0-14%). Rates of biochemical improvement (27-100%) and symptom improvement (23-100%) ranged widely depending on the population studied and the definition of response. The most common toxicities were fatigue, diarrhoea, abdominal discomfort and cholelithiasis, with no severe or unexpected toxicities compared to standard-dose somatostatin analogues. Conclusion(s): The current evidence indicates that escalated-dose somatostatin analogues are well-tolerated in patients with gastroenteropancreatic neuroendocrine tumours, with significant rates of disease control but low rates of tumour response. It was difficult to judge the exact rate of biochemical response or symptomatic improvement. There is a need for large, prospective studies investigating the role of escalated-dose somatostatin analogues in the treatment of metastatic gastroenteropancreatic neuroendoc

The beneficial effects of two probiotic bacteria, Bacillus licheniformis and Bacillus megaterium, on growth, biochemical, and immunological responses of Litopenaeus vannamei (Boone, 1931) were evaluated both individually and in combination. A 60 day experimental trial was conducted on 1200 post larvae (PL) of Litopenaeus vannamei divided into four experimental groups, with three replicates of each treatment, and 100 PL in each replicate. The shrimp were fed a commercial diet (32% protein) supplemented with different probiotics. The first treatment included only B. licheniformis @ ~ 1x 108 cfu/kg diet (T1), the second consisted of a combination of ~ 0.5 x 108 cfu/kg of B. licheniformis mixed with a similar concentration of B. megaterium (T2), and the third had only B. megaterium @ ~1x 108 cfu/kg diet (T3). The control diet (C) had neither of the probiotic bacteria. Growth performance, biochemical, and immunological parameters of experimental shrimp were measured at 20 day intervals. Probiotic fed shrimp showed significantly higher growth, biochemical, and immunological response than the control. Among the probiotic treatments the mixture of B. licheniformis and B. megaterium (T2) performed better than the individual probiotics alone, indicating the synergistic effect of these two functionally different probiotics