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2023 ◽  
Vol 83 ◽  
A. A. Banjabi ◽  
K. Kannan ◽  
T. A. Kumosani ◽  
J. M. Yousef ◽  
K. O. Abulnaja ◽  

Abstract Serum toxic metals have been implicated in development of many diseases. This study investigated the association between blood levels of lead and cadmium with abnormal bone mineral density (BMD) and incidence of osteoporosis. Sixty Saudi male adults age matching were assigned into two groups: A healthy control group (n = 30) and osteoporosis patients diagnosed according to T-score (n = 30). Serum calcium, vitamin D, osteocalcin, lead, cadmium were measured. Osteoporotic group showed a highly significant elevation of blood lead and cadmium levels compared to the control group (p <0.001). BMD was negatively correlated with serum osteocalcin level compared with control. There was a significant negative correlation between the cadmium and lead levels (r=-0.465 and p-value = 0.01) and calcium (p < 0.004). Our findings suggested that high cadmium and lead were negative correlated to BMD and increased the risk factor for osteoporosis.

2022 ◽  
Vol 9 ◽  
Christine Kim ◽  
Pahriya Ashrap ◽  
Deborah J. Watkins ◽  
Bhramar Mukherjee ◽  
Zaira Y. Rosario-Pabón ◽  

Background/Aim: The association between heavy metal exposure and adverse birth outcomes is well-established. However, there is a paucity of research identifying biomarker profiles that may improve the early detection of heavy metal-induced adverse birth outcomes. Because lipids are abundant in our body and associated with important signaling pathways, we assessed associations between maternal metals/metalloid blood levels with lipidomic profiles among 83 pregnant women in the Puerto Rico PROTECT birth cohort.Methods: We measured 10 metals/metalloid blood levels during 24–28 weeks of pregnancy. Prenatal plasma lipidomic profiles were identified by liquid chromatography–mass spectrometry-based shotgun lipidomics. We derived sums for each lipid class and sums for each lipid sub-class (saturated, monounsaturated, polyunsaturated), which were then regressed on metals/metalloid. False discovery rate (FDR) adjusted p-values (q-values) were used to account for multiple comparisons.Results: A total of 587 unique lipids from 19 lipid classes were profiled. When controlling for multiple comparisons, we observed that maternal exposure to manganese and zinc were negatively associated with plasmenyl-phosphatidylethanolamine (PLPE), particularly those containing polyunsaturated fatty acid (PUFA) chains. In contrast to manganese and zinc, arsenic and mercury were positively associated with PLPE and plasmenyl-phosphatidylcholine (PLPC).Conclusion: Certain metals were significantly associated with lipids that are responsible for the biophysical properties of the cell membrane and antioxidant defense in lipid peroxidation. This study highlighted lipid-metal associations and we anticipate that this study will open up new avenues for developing diagnostic tools.

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 173
Maria Klomp ◽  
Leo Hofland ◽  
Lilian van den Brink ◽  
Peter van Koetsveld ◽  
Fadime Dogan ◽  

Background: To improve peptide receptor radionuclide therapy (PRRT), we aimed to enhance the expression of somatostatin type-2 receptors (SSTR2) in vitro and in vivo, using valproic acid (VPA). Methods: Human NCI-H69 small-cell lung carcinoma cells were treated with VPA, followed by [111In]In-DOTATATE uptake studies, RT-qPCR and immunohistochemistry analysis. Furthermore, NCI-H69 xenografted mice were treated with VPA or vehicle, followed by [177Lu]Lu-DOTATATE injection. Biodistribution studies were performed, and tissues were collected for further analysis. Results: VPA significantly increased SSTR2 expression in vitro. In animals, a statistically significant increased [177Lu]Lu-DOTATATE tumoral uptake was observed when VPA was administered eight hours before [177Lu]Lu-DOTATATE administration, but increased tumor SSTR2 expression levels were lacking. The animals also presented significantly higher [177Lu]Lu-DOTATATE blood levels, as well as an elevated renal tubular damage score. This suggests that the enhanced tumor uptake was presumably a consequence of the increased radiotracer circulation and the induced kidney damage. Conclusions: VPA increases SSTR2 expression in vitro. In vivo, the observed increase in tumoral [177Lu]Lu-DOTATATE uptake is not caused by SSTR2 upregulation, but rather by other mechanisms, e.g., an increased [177Lu]Lu-DOTATATE circulation time and renal toxicity. However, since both drugs are safely used in humans, the potential of VPA to improve PRRT remains open for investigation.

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262544
Annalisa Trecarichi ◽  
Natalie A. Duggett ◽  
Lucy Granat ◽  
Samantha Lo ◽  
Afshan N. Malik ◽  

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side effect of several first-line chemotherapeutic agents including paclitaxel, oxaliplatin and bortezomib, for which no predictive marker is currently available. We have previously shown that mitochondrial dysfunction is associated with the development and maintenance of CIPN. The aim of this study was to evaluate the potential use of mitochondrial DNA (mtDNA) levels and complex I enzyme activity as blood biomarkers for CIPN. Real-time qPCR was used to measure mtDNA levels in whole blood collected from chemotherapy- and vehicle-treated rats at three key time-points of pain-like behaviour: prior to pain development, at the peak of mechanical hypersensitivity and at resolution of pain-like behaviour. Systemic oxaliplatin significantly increased mtDNA levels in whole blood prior to pain development. Furthermore, paclitaxel- and bortezomib-treated animals displayed significantly higher levels of mtDNA at the peak of mechanical hypersensitivity. Mitochondrial complex I activity in whole blood was assessed with an ELISA-based Complex I Enzyme Activity Dipstick Assay. Complex I activity was not altered by any of the three chemotherapeutic agents, either prior to or during pain-like behaviour. These data demonstrate that blood levels of mtDNA are altered after systemic administration of chemotherapy. Oxaliplatin, in particular, is associated with higher mtDNA levels before animals show any pain-like behaviour, thus suggesting a potential role for circulating mtDNA levels as non-invasive predictive biomarker for CIPN.

Khaled Abdalla Abd-Elbaseer ◽  
Eman Ahmed Abd-Elmawgood ◽  
H. M. Qubaisy ◽  
Yaser F. Abd-Elraheem ◽  
Abdel-Rahman Abdel-Hamed El-Saied ◽  

Scorpion envenomation is a life-threatening emergency and causes serious health problems in tropical and subtropical regions. The aim of this study was to correlate the serum levels of biochemical parameters at admission in children with scorpion envenomation with subsequent morbidity and mortality. It was a prospective, observational, and descriptive study conducted for scorpion-envenomed children who presented to emergency and intensive care units between April 2019 and September 2019. Demographic, clinical, and laboratory findings of patients were recorded and tabulated. Routine investigations were done for all patients in addition to blood levels of lactate, free fatty acids (FFA), and insulin. All patients were compared according to outcome as survivors and nonsurvivors and according to glucose level as normoglycemic and hyperglycemic groups. There were 62 scorpion sting cases; their mean age was 8.6 ± 3.2 years. Patients aged more than 6 years (74.2%), and males (66.1%) were more affected than others. As regards severity, 25.8% were suffering organ dysfunction, 40.3% suffered systemic manifestations without organ dysfunction, and (33.9%) with only local manifestations. Serum glucose and FFA were significantly higher in nonsurvivors compared with survivors. Shock, convulsion, coma, heart failure, and pulmonary edema were significantly more common in hyperglycemic than normoglycemic group. Hyperglycemia, and raised FFA were associated with severe scorpion envenomation. Raised FFA was well correlated with presence of heart failure, leucocytosis, and hyperglycemia. Adding serum glucose and FFA to monitoring parameters of scorpionism severity can help the prediction of high-risk patients.

2022 ◽  
Vol 43 (1) ◽  
pp. 73-90
Tiago Pereira Guimarães ◽  
Ubirajara Oliveira Bilego ◽  
Pedro Leonardo de Paula Rezende ◽  
Wescley Faccini Augusto ◽  

The aim of this study was to evaluate the performance of young bulls from three genetic groups, ½ Brangus x ½ Nellore (BRN), Nellore (NEL) and ½ Canchim x ½ Nellore (CAN), reared on pasture and supplemented with mineral (MS) or energy-mineral (MES) supplement. Eighty-one bulls, with a mean age of 12 months and mean body weight of 252 ± 33 kg were used. The experiment was conducted in a 3x2 factorial completely randomized design. Each genetic group was subdivided into six experimental plots, three received MS and three received MES. Animals were managed in a rotational stocking system in a Tifton 85 grass pasture. The consumption of MS was similar between the genetic groups with an average of 0.073 kg animal-1 day-1, whereas the consumption of MES was higher for BRN, 2.10 kg animal-1 day-1, followed by CAN, with 1.57 kg animal-1 day-1, and lower for NEL, with 1.28 kg animal-1 day-1. The average daily weight gain (ADG) was greater for animals that received MES compared to those that were given MS. For animals that received MS, the BRN group had ADG of 0.64 kg animal-1, while the NEL and CAN groups were similar with a mean of 0.46 kg animal-1. For animals that received MES, the CAN group had higher ADG, 0.97 kg animal-1, while the NEL and BRN groups were similar, with an average of 0.86 kg animal-1. Blood levels of total protein, albumin, creatinine, glucose and cholesterol did not change depending on the types of supplements used or between genetic groups. Higher serum urea levels were observed in NEL and CAN animals that received MS. Serum aspartate aminotransferase levels were higher in BRN and CAN animals that received MES. Gains in rump height, height at the withers, body length, rump width and chest perimeter were greater in animals that received MES. Mostly, the gains in morphometric measurements were greater for crossbred animals than for the NEL group. The supply of mineral-energy supplement in Tifton 85 grass pasture during the rainy season is recommended only for Nellore and ½ Canchim x ½ Nellore young bulls. Crossbred young bulls show greater gains in morphometric measurements than Nellore young bulls during rearing.

Fishes ◽  
2022 ◽  
Vol 7 (1) ◽  
pp. 14
Takeshi Miura ◽  
Munenori Nishikawa ◽  
Yuki Otsu ◽  
Muhammad Fariz Zahir Ali ◽  
Atsushi Hashizume ◽  

The effect of silkworm-derived polysaccharide silkrose on fish ectoparasites was investigated. When juvenile yellowtail (Seriola quinqueradiata) fed diets containing silkrose were artificially infected with Benedenia seriolae, a fish ectoparasite, the numbers of parasitized B. seriolae were significantly lower compared to that in fish in the control group without silkrose treatment. Furthermore, when juvenile yellowtails were severely infected with B. seriolae, no mortality was observed in the silkrose-treated group, compared to more than 60% in the control group. In field studies carried out at a fish farm with yellowtail and white trevally (Pseudocaranx dentex), oral treatment with silkrose significantly reduced B. seriolae parasitism in yellowtail and Caligus longipedis and Neobenedenia girellae parasitism in white trevally. Silkrose treatment also reduced blood levels of cortisol, a stress hormone in both species. The changes in gene expression in the epidermis of yellowtail by silkrose treatment were also investigated, showing that the expression of various genes, including factors involved in immunity, stress response, and wound healing, was changed by the treatment. These findings indicate that silkworm-derived silkrose effectively prevents infection by external parasites in yellowtail and white trevally.

2022 ◽  
Vol 21 (1) ◽  
André Daher ◽  
Douglas Pereira Pinto ◽  
Laís Bastos da Fonseca ◽  
Heliana Martins Pereira ◽  
Diego Medeiros Dias da Silva ◽  

Abstract Background Vivax malaria is a neglected disease. There is an irrefutable need for better treatments with higher acceptability and efficacy. The treatment efficacy is influenced by many factors, including bioavailability. Hence, a straightforward strategy to improve vivax malaria treatment efficacy is the deployment of good quality formulations of primaquine and chloroquine. As these treatments were developed more than 70 years ago, many of the available data on blood levels of both drugs are based on obsolete analytical methodologies or pharmaceutical formulations, which are not available anymore. Herein, the results of three bioequivalence studies are presented, providing individual pharmacokinetic data on chloroquine and primaquine of more than a hundred healthy volunteers and using up-to-date analytical methods. Methods Three trials were designed as a single centre, randomized, single dose, open label, fasting, crossover bioequivalence studies comparing a new coated chloroquine tablet to the uncoated tablet, and 5 and 15 mg primaquine formulations to either an international reference product or the currently distributed tablets. Plasma concentrations of chloroquine and primaquine were measured using a validated HPLC–MS/MS method in accordance with current international regulatory requirements for bio-analytical methods. Results In total, a hundred eleven healthy volunteers of both genders were included in the three studies (n = 32; 30 and 56 respectively). No serious adverse events occurred. Drugs levels were measured in 5,520 blood samples. The estimated ratio of the geometric means of Cmax, AUC0-t and AUC0-inf of test and reference drugs and their 90% CI for chloroquine 150 mg, primaquine 15 mg and primaquine 5 mg were: 95.33% (89.18; 101.90), 86. 85% (82.61; 91.31), and 84.45% (76.95; 92.67); 93.28% (81.76; 106.41), 94.52% (86.13; 103.73) and 93.93% (85.83; 102.79); 97.44% (90.60; 104.78), 93.70% (87.04; 100.87) and 91.36% (85.27; 97.89), respectively. As Cmax and AUC0-t 90% CI were within the acceptance interval of 80–125% in all cases, the formulations tested were bioequivalent. Conclusions In conclusion, the three studies provided detailed chloroquine and primaquine pharmacokinetic data in accordance with current regulatory standards. Together with other open data initiatives, this individual data may increase the accuracy of pharmacokinetic models guiding best dose, new combinations, regimens and formulations to optimize the current chloroquine and primaquine treatments for vivax malaria. The data presented here may support the deployment of high-quality drugs and evidence-based public health policies.

2022 ◽  
Ryan Drenan ◽  
Xiao-Tao Jin ◽  
Brenton Tucker ◽  
Leanne Thomas ◽  
Noah Walker ◽  

Many tobacco smokers consume nicotine intermittently, but the underlying mechanisms and neurobiological changes associated with intermittent nicotine intake are unclear. Understanding intermittent nicotine intake is a high priority, as it could promote therapeutic strategies to attenuate tobacco consumption. We examined nicotine intake behavior and neurobiological changes in male rats that were trained to self-administer nicotine during brief (5 min) trials interspersed with longer (15 min) drug-free periods. Rats readily adapted to intermittent access (IntA) SA following acquisition on a continuous access (ContA) schedule. Probabilistic analysis of IntA nicotine SA suggested reduced nicotine loading behavior compared to ContA, and nicotine pharmacokinetic modeling revealed that rats taking nicotine intermittently may have increased intake to maintain blood levels of nicotine that are comparable to ContA SA. After IntA nicotine SA, rats exhibited an increase in unreinforced responses for nicotine-associated cues (incubation of craving) and specific alterations in the striatal proteome after 7 days without nicotine. IntA nicotine SA also induced nAChR functional upregulation in the interpeduncular nucleus (IPN), and it enhanced nicotine binding in the brain as determined via [11C]nicotine positron emission tomography. Reducing the saliency of the cue conditions during the 5 min access periods attenuated nicotine intake, but incubation of craving was preserved. Together, these results indicate that IntA conditions promote nicotine SA and nicotine seeking after a nicotine-free period.

2022 ◽  
pp. 95-104
E. Yu. Plotnikova ◽  
M. N. Sinkova ◽  
L. K. Isakov

Asthenia and fatigue are the most common syndromes in patients with liver disease, which significantly affects their quality of life. The prevalence of fatigue in chronic liver diseases is from 50% to 85%. While some progress has been made in understanding the processes that can cause fatigue in general, the underlying causes of fatigue associated with liver disease remain not well understood. In particular, many data suggest that fatigue associated with liver disease likely results from changes in neurotransmission in the brain against the background of hyperammonemia. Hyperammonemia is a metabolic state characterized by an increased level of  ammonia, a  nitrogen-containing compound. The  present review describes hyperammonemia, which is likely important in the pathogenesis of fatigue associated with liver disease. Ammonia is a potent neurotoxin, its elevated blood levels can cause neurological signs and symptoms that can be acute or chronic, depending on the  underlying pathology. Hyperammonemia should be recognized early, and immediately treated to prevent the development of life-threatening complications, such as, swelling of the brain and coma. The article gives pathophysiological mechanisms of influence of hyperammonemia on state of psychovegetative status of patients with liver diseases, also lists basic principles of treatment. A significant part of the article is devoted to L-ornithine-L-aspartate, which is effective in asthenia and fatigue to reduce the level of hyperammonemia through a variety of well-studied mechanisms in chronic liver diseases.

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