Accidental poisonings by ingesting conjunctival fluid mixed with eye drops commonly involve alpha-2 adrenergic receptor agonists and tetrahydrozoline. These substances are recognized in commonly ...reported ingestions. Victims of all ages, otherwise in good health, often present as pale and lethargic to the emergency department (ED) after unintentionally ingesting topical eye medication. While eye drop poisoning cases in childhood include accidents during the play and poisonings in adults mean either suicide attempts or side effects caused by the systemic absorption of the substance, fluid of the ocular surface is a risk to all age groups. With this in mind, this study aimed to summarize data in the literature on tetrahydrozoline and alpha-2 adrenergic receptor agonists as dangerous medications, even when administered in low-bioavailability forms, such as eye drops. With this aim, a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review of relevant studies was conducted. A search of PubMed, Scopus, Web of Science, and EBSCOhost yielded nine studies that met the rigorous inclusion criteria. The primary studies were subject to a meta-analysis once a quality appraisal of the studies and a narrative synthesis of the extracted data had been conducted. The author hopes that this information will provide observations that will lead to better designs for over-the-counter eye drops, off-label drug usage policies, and parental attention.
Chagas disease is caused by
and represents a major public health problem, which is endemic in Latin America and emerging in the rest of the world. The two drugs that are currently available for its ...treatment, Benznidazole and Nifurtimox, are partially effective in the chronic phase of the disease. In this study, we designed and synthesized the benzyl ester of N-isopropyl oxamic acid (B-NIPOx), which is a non-polar molecule that crosses cell membranes. B-NIPOx is cleaved inside the parasite by carboxylesterases, releasing benzyl alcohol (a molecule with antimicrobial activity), and NIPOx, which is an inhibitor of α-hydroxy acid dehydrogenase isozyme II (HADH-II), a key enzyme in
metabolism. We evaluated B-NIPOx cytotoxicity, its toxicity in mice, and its inhibitory activity on purified HADH-II and on
homogenates. We then evaluated the trypanocidal activity of B-NIPOx in vitro and in vivo and its effect in the intestine of
-infected mice. We found that B-NIPOx had higher trypanocidal activity on epimastigotes and trypomastigotes than Benznidazole and Nifurtimox, that it was more effective to reduce blood parasitemia and amastigote nests in infected mice, and that, in contrast to the reference drugs, it prevented the development of Chagasic enteropathy.
Abstract
BACKGROUND AND IMPORTANCE
The standard clinical technique for repairing peripheral nerve gaps is the use of autologous sensory nerve grafts. The present study tested whether a collagen tube ...filled with autologous platelet-rich fibrin could induce sensory and motor recovery across a 12-cm nerve gap repaired 3.25 years post trauma, and reduce or eliminate neuropathic pain.
CLINICAL PRESENTATION
Two years postrepair, good ring and small finger motor function had developed that could generate 1 kg of force, and topographically correct 2-point discrimination and sensitivity to vibration in the small and ring finger and proximal but not distal wrist had developed. The patient's excruciating neuropathic pain was reduced to tolerable, and he avoided the indicated extremity amputation. The 12-cm-long nerve gap was bridged with a collagen tube filled with autologous platelet-rich fibrin.
CONCLUSION
We demonstrate that a conduit filled with platelet-rich fibrin can induce limited, but appropriate, sensory and motor recovery across a 12-cm nerve gap repaired 3.25 years post trauma, without sacrificing a sensory nerve, can reduce existing excruciating neuropathic pain to tolerable, and allow avoidance of an indicated upper-extremity amputation. We believe the technique can be improved to induce more extensive and reliable neurological recovery.
Background
We aimed to determine if there was a higher incidence of small intestinal bacterial overgrowth (SIBO) in non‐alcoholic fatty liver disease (NAFLD) than in patients without NAFLD. Moreover, ...we assessed whether patients with significant fibrosis (SF) had a higher incidence of SIBO compared with patients with non‐significant or no liver fibrosis.
Methods
NAFLD was diagnosed in 117 patients by using Fibroscan with a controlled attenuation parameter (CAP) as well as liver biopsy (LB). SIBO was defined by esophagogastroduodenoscopy with an aspiration of the descending duodenum.
Results
Patients with non‐alcoholic steatohepatitis (NASH) and those with SF on LB had a significantly higher incidence of SIBO than patients without NASH and those without SF, respectively (P < .05). According to histological characteristics, there was a higher proportion of patients in the SIBO group with higher steatosis and fibrosis grade, lobular and portal inflammation, and ballooning grade (P < .001). In multivariate analysis, significant predictors associated with SF and NASH were type 2 diabetes mellitus (T2DM) and SIBO. Moreover, in multivariate analysis, significant predictors that were independently associated with SIBO were T2DM, fibrosis stage and ballooning grade (OR 8.80 (2.07‐37.37), 2.50 (1.16‐5.37) and 27.6 (6.41‐119), respectively). The most commonly isolated were gram‐negative bacteria, predominantly Escherichia coli and Klebsiella pneumoniae.
Conclusion
In this relatively large population of patients, we used a gold standard for both SIBO (quantitative culture of duodenum's descending part aspirate) and NAFLD (LB), and we demonstrated that NASH patients and those with SF had a higher incidence of SIBO. Moreover, significant predictors independently associated with SIBO were T2DM, fibrosis stage and ballooning grade. Although TE is a well‐investigated method for steatosis and fibrosis detection, in our study, independent predictors of SIBO were histological characteristics of NAFLD, while elastographic parameters did not reach statistical significance.
This study aimed to investigate the impact of the cornea’s biomechanical properties, corneal hysteresis (CH), and corneal resistance factor (CRF) on postoperative astigmatism after cataract surgery ...and determine the other factors that influence it. Forty eyes of 40 patients (13M/27F; the median age of 74) were included in this prospective study, underwent 2.75 mm incision cataract surgery, and were followed for 30 days. Visits were scheduled at baseline before surgery (V0), the 1st (V1), the 7th (V2), and the 30th (V3) postoperative days. The main parameters estimated and analyzed with Statistica® 14.0.1 were CH, CRF, astigmatism diopter, and axis. Following the cataract surgery, the CH did not significantly change during the study visits (p = 0.109). However, there was a significant change in the CRF from baseline during the study visits (per protocol set) (p = 0.002). After a slight but insignificant increase from V0 to V1, post hoc analysis found a significant decrease in the mean CRF from V1 to V2 (p = 0.049) with no substantial change from V2 to V3. According to the post hoc analysis, the median astigmatism diopter increased significantly only from V0 to V1 (p = 0.001) and slightly but not significantly decreased to the end of the study with the achievement of a near-baseline value. The main predictors for the final astigmatism diopter (R2 = 0.898) obtained by stepwise regression analysis were its values at V0, V1, and V2 (p < 0.001). The CRF at V1 was marginally significant, with a negative parameter estimate of −0.098303 (p = 0.0623). In conclusion, there was no correlation between preoperative CH and CRF and postoperative astigmatism using 2.75 mm incision cataract surgery. However, the final astigmatism diopter’s main predictors were its baseline values before cataract surgery, the first, and the seventh postoperative days.
Glycoconjugate vaccines provide effective prophylaxis against bacterial infections. To date, however, no commercial vaccine has been available in which the key carbohydrate antigens are produced ...synthetically. We describe the large-scale synthesis, pharmaceutical development, and clinical evaluation of a conjugate vaccine composed of a synthetic capsular polysaccharide antigen of Haemophilus influenzae type b (Hib). The vaccine was evaluated in clinical trials in Cuba and showed long-term protective antibody titers that compared favorably to licensed products prepared with the Hib polysaccharide extracted from bacteria. This demonstrates that access to synthetic complex carbohydrate-based vaccines is feasible and provides a basis for further development of similar approaches for other human pathogens.
Although the eye can be subjected to therapeutic manipulation, some of its structures are highly inaccessible. Thus, conventional therapeutic administration pathways, such as topical or systemic ...routes, usually show significant limitations in the form of low ocular penetration or the appearance of side effects linked to physiology, among others. The critical feature of many xenobiotics is the drug gradient from the concentrated tear reservoir to the relatively barren corneal and conjunctival epithelia, which forces a passive route of absorption. The same is true in the opposite direction, towards the ocular surface (OS). With the premise that tears can be regarded as equivalent to or a substitute for plasma, researchers may determine drug concentrations in the OS fluid. Within this framework, a survey of scholarly sources on the topic was conducted. It provided an overview of current knowledge, allowing the identification of relevant theories, methods, and gaps in the existing research that can be employed in subsequent research. OS fluid (tears particularly) has enormous potential as a source of biological material for external drug screening and as a biomarker of various systemic diseases. Given the numerous alternate matrices, knowledge of their properties is very important in selecting the most appropriate specimens in toxicological analyses.
Auto-brewery syndrome (ABS), also called gut fermentation syndrome, is an extremely infrequent but also underrecognized disorder where ethanol is produced endogenously, similar to a typical ...bioreactor. The reliability of forensic alcohol analysis results is frequently challenged as the ethanol concentration in the breath, blood, and/or urine constitutes important evidence for prosecuting drivers under the influence of the alcohol. This further emphasizes the need to understand ABS, as in legal proceedings it is often presented as grounds for acquittal due to the concept that the findings could have corresponded to endogenously produced ethanol. However, this rare and underdiagnosed medical condition should not be considered as purely a lawyer’s favorite argument. Manifestations of ABS can have a severe impact on a patient’s life and pose social consequences as well. Unfortunately, barely anything has been unearthed, and aspects such as genetic susceptibility, gut-mucus-eating microorganisms, and fecal microbiome transplantation were reviewed for the first time in this context. The framework of this review was not limited to the gut microbiota exclusively; moreover, the overgrowth of microorganisms is linked to the use of antibiotics. Studies have indicated that carbohydrate fermentation occurs in locations other than in intra-intestinal flora. Accordingly, the literature was searched for cases of patients with ABS with yeast infections in their genitourinary or oral systems.
Quetiapine is a second-generation antipsychotic drug available for two and half decades. Due to increased misuse, prescription outside the approved indications, and availability on the black market, ...it is being encountered in medicolegal autopsies more frequently. For instance, it has been linked to increased mortality rates, most likely due to its adverse effects on the cardiovascular system. Its pharmacokinetic features and significant postmortem redistribution challenge traditional sampling in forensic toxicology. Therefore, a systematic literature review was performed, inclusive of PubMed, the Web of Science-core collection, and the Scopus databases; articles were screened for the terms "quetiapine", "death", and "autopsy" to reevaluate each matrix used as a surrogate endpoint in the forensic toxicology of quetiapine-related deaths. Ultimately, this review considers the results of five studies that were well presented (more than two matrices, data available for all analyses, for instance). The highest quetiapine concentrations were usually measured in the liver tissue. As interpreted by their authors, the results of the considered studies showed a strong correlation between some matrices, but, unfortunately, the studies presented models with poor goodness of fit. The distribution of quetiapine in distinct body compartments/tissues showed no statistically significant relationship with the length of the postmortem interval. Furthermore, this study did not confirm the anecdotal correlation of peripheral blood concentrations with skeletal muscle concentrations. Otherwise, there was no consistency regarding selecting an endpoint for analysis.
