Progress in the Use of Glucocorticoids and Biological Agents in Non-Infectious Uveitis

One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.

Biologics in non-infectious uveitis past,present and future

Our increase in knowledge of the pathophysiology of non-infectious uveitis(NIU)and other immune-mediated diseases has been mirrored over the last two decades by the expansion of therapeutic options in the realm of immunosuppressive medications.Principal among these advances is the emergence of biologics,which offer the promise of targeted therapy and the hope of reduced toxicity when compared to corticosteroids and“standard”immunosuppression.Among the biologics,monoclonal antibodies blocking tumor necrosis factor alpha(TNF-α)have been shown to be a very effective therapeutic target for uveitis and many associated systemic inflammatory diseases.Multiple TNF blockers have shown benefit for uveitis,and in 2016,adalimumab became the first biologic and non-corticosteroid immunosuppressive to obtain Food and Drug Administration(FDA)approval in the treatment of NIU.Although effective,TNF blockers are not universally so,and safety concerns such as infection and demyelinating disease must be carefully considered and ruled out prior to their use,especially in patients with intermediate uveitis with which multiple sclerosis is a known association.Ongoing study has identified novel targets for regulation in the treatment of immune-mediated and inflammatory diseases.Interferons,interleukin and Janus kinase inhibitors in addition to antibodies targeting T cell and B cell activation highlight the expanding field of treatment modalities in NIU.Ongoing study will be required to better determine the safety and efficacy of biologics in the armamentarium of immunosuppressive treatments for NIU.

Non-Infectious Complications of Peritoneal Dialysis in Senegal

Introduction: Senegal has pioneered the implementation of peritoneal dialysis (PD) in West Africa, practicing it since 2004. Non-infectious complications are a significant cause of failure of this technique and the transfer of patients to haemodialysis. The aim of this study was to determine the prevalence and the different types of non-infectious complications in our context. Patients and Methods: This was a 5-year, descriptive, retrospective study of patients on chronic peritoneal dialysis for more than 3 months. Results: During the study period, 75 patients were included. The prevalence of non-infectious complications was 88%, including 45.3% mechanical complications and 76% metabolic complications. Catheter migration was the most common mechanical complication (55.9%), followed by catheter blockage (23.5%). Metabolic complications were dominated by hypoalbuminemia (76.3%). Dyslipidaemia and hypokalaemia affected more than 50% of patients, occurring in 59.3% and 56.9% of cases, respectively. Conclusion: In our study, non-infectious complications related to PD were frequent and varied. They remain a significant cause of technical failure. Mechanical complications are often the cause of permanent transfer to haemodialysis.

First identification of a novel Aichivirus D in goats with diarrhea

Kobuvirus comprises 6 officially recognized species,namely Aichivirus A-F,and can be further divided into 20 genotypes through VP1 gene phylogenetic analysis(https://ictv.global/report/chapter/picornaviridae/picornaviridae/kobuvirus).Aichivirus A in human,Aichivirus B in bovine,Aichivirus C in porcine and caprine,Aichivirus D in yak have been proved to be associated with diarrhea(Chen Y S et al.2013;Yang et al.2015;Zhu et al.2016;Zhai et al.2017;Wang et al.2020;Abi et al.2022;Yan et al.2023).

The protective role of prebiotics and probiotics on diarrhea and gut damage in the rotavirus-infected piglets

Rotavirus is one of the pathogenic causes that induce diarrhea in young animals, especially piglets, worldwide. However, nowadays, there is no specific drug available to treat the disease, and the related vaccines have no obvious efficiency in some countries. Via analyzing the pathogenesis of rotavirus, it inducing diarrhea is mainly due to disturb enteric nervous system, destroy gut mucosal integrity, induce intracellular electrolyte imbalance, and impair gut microbiota and immunity. Many studies have already proved that prebiotics and probiotics can mitigate the damage and diarrhea induced by rotavirus infection in hosts. Based on these, the current review summarizes and discusses the effects and mechanisms of prebiotics and probiotics on rotavirus-induced diarrhea in piglets. This information will highlight the basis for the swine production utilization of prebiotics and probiotics in the prevention or treatment of rotavirus infection in the future.

Structure and Composition of Non-Infectious Phosphate Calculi Formed in Patients with Low and High Urinary Phosphate Concentrations

Objective: The aim of this paper was to assess the relationships among chemical, phase and structural composition and?etiopathogenic factors of non-infectious phosphate calculi formed in patients with low and high urinary phosphate concentrations, and to characterize the mechanism of their formation related on biochemical results. Material and Methods: Twelve samples of phosphate renal calculi were obtained, 4 from patients with low phosphaturia and 6 from patients with high urinary phosphate concentrations. Their chemical composition was determined qualitatively by energy dispersive X-ray analysis and quantitatively by spectrophotometric and thermal analysis;and their phase composition was determined by Fourier transform infrared transmission spectroscopy and X-ray diffraction. The structure of the calculi was assessed by scanning electron microscopy. Results: Non-infectious phosphate renal calculi of patients with low phosphaturia consist of poorly crystalline carbonate hydroxyapatite, whereas those of patients with high urinary phosphate concentrations consist of poorly crystalline hydroxyapatite with some amount of calcium oxalate crystals. Calculi of patients with high urinary phosphate concentrations are formed at urinary supersaturation with respect to hydroxyapatite and calcium oxalate about 4 times higher than in patients with low phosphaturia. Conclusion: In patients with low phosphaturia, the non-infectious phosphate renal calculi are formed in urine near pH 7 and contain only poorly crystalline carbonate hydroxyapatite. In patients with high urinary phosphate concentrations and hypercalciuria, the calculi are formed in urine near pH 6 and consist of both poorly crystalline hydroxyapatite and some amount of calcium oxalate crystals.

Lactose-free milk powder can effectively relieve diarrhea symptoms in weaning SD rats and children

Diarrhea has become the leading cause of illness and death among infants and young children in developing countries.Clinically,patients with diarrhea showed damaged intestinal epithelial villi,usually accompanied by lactase deficiency.In this study,we evaluated the therapeutic effects of lactose-free milk powder on rats and children with diarrhea.Antibiotic-associated diarrhea(AAD)model was established by gavage with antibiotic mixture in SD rats,followed by administration of milk powder containing lactose or not.The results showed that lactose-free milk powder ameliorated A AD-related diarrhea symptoms,and accelerated the recovery from diarrhea.And 16S sequencing results indicated lactose-free milk powder contributed to increase theα-andβ-diversity of intestinal flora,and restore the intestinal microbiota disorder.In conclusion,our data demonstrate that lactose-free milk powder could alleviate diarrhea by restoring gut microbiota and intestinal barrier function.

A CRISPR/Cas12a-based platform for rapid on-site bovine viral diarrhea virus diagnostics

Bovine viral diarrhea virus(BVDV)is a positive-sense single-stranded RNA virus,belonging to the genus Pestivirus in the Flaviviridae family(Riitho et al.2020).Currently,BVDV is divided into 3 main genotypes,BVDV-1,BVDV-2,and BVDV-3,based on the genetic differences in the 5′untranslated region(5′UTR)(Muasya et al.2022).

Transcriptome analysis suggests broad jejunal alterations in Linghu’s obesity-diarrhea syndrome:A pilot study

BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as Linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely unknown.AIM To reveal the transcriptomic changes in the jejunum involved in ODS.METHODS In a cohort of 6 ODS patients(JOD group),6 obese people without diarrhea(JO group),and 6 healthy controls(JC group),high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes.In another cohort of 16 ODS patients(SOD group),16 obese people without diarrhea(SO group),and 16 healthy controls(SC group),serum diamine oxidase(DAO)and D-lactate(DLA)concentrations were detected to assess changes in intestinal barrier function.RESULTS The gene expression profiles of jejunal mucosa in the JO and JC groups were similar,with only 1 differentially expressed gene(DEG).The gene expression profile of the JOD group was significantly changed,with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group,129 of which overlapped.The enrichment analysis of these DEGs showed that the biological processes such as digestion,absorption,and transport of nutrients(especially lipids)tended to be up-regulated in the JOD group,while the biological processes such as rRNA processing,mitochondrial translation,antimicrobial humoral response,DNA replication,and DNA repair tended to be down-regulated in the JOD group.Eight DEGs(CDT1,NHP2,EXOSC5,EPN3,NME1,REG3A,PLA2G2A,and PRSS2)may play a key regulatory role in the pathological process of ODS,and their expression levels were significantly decreased in ODS patients(P<0.001).In the second cohort,compared with healthy controls,the levels of serum intestinal barrier function markers(DAO and D-LA)were significantly increased in all obese individuals(P<0.01),but were higher in the SOD group than in the SO group(P<0.001).CONCLUSION Compared with healthy controls and obese individuals without diarrhea,patients with Linghu’s ODS had extensive transcriptomic changes in the jejunal mucosa,likely affecting intestinal barrier function and thus contributing to the obesity and chronic diarrhea phenotypes.

Frequency of Rotavirus among under 5 Children Admitted to Wad Madani Pediatric Teaching Hospital with Diarrhea, Gezira State, Sudan (2021-2022)

Rotavirus is the leading cause of acute gastroenteritis and responsible for 20% of death in children under 5 years of age approximately 111 million episodes of gastroenteritis due to Rotavirus in under 5 children, which result in 25 million visits to clinic, 2 million hospitalization and 352,000 - 592,000 deaths. Children in the poorest countries account 82% of rotaviruses death. Diarrhea disease are major cause of death and disease among children under five years, a child on average suffers 2 to 3 attacks of diarrhea every year. Stools samples were collected from 196 children suffering from diarrhea and were tested for rotaviruses by immune chromatography test antigen (ICT-Ag), ELISA and RT PCR The data were analyzed using statistical package for the Social Sciences (SPSS). The results showed that prevalence of rotavirus was 26/196 (13.3%) by ICT Ag and ELISA and confirmed by RT-PC R. 87.8% of the children were vaccinated by Rota vaccine, 70% of their mothers not using soap for cleaning the children and thought diarrhea not infectious disease and believed it was caused by teething. In conclusion there was a decrease in prevalence of diarrhea by Rotavirus due to insertion of Rota vaccine in routine vaccination, rotavirus infection mostly occurs in poor family that not able to provide safe water and due to poor sanitation and low education of mother beside that some children suffered from malnutrition, so it recommended to incorporate ELISA as a diagnostic tool in routine diagnosis of rotavirus among children suffered from gastroenteritis.

Calcium/calcimimetic via calcium-sensing receptor ameliorates cholera toxin-induced secretory diarrhea in mice

BACKGROUND Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system.Calcium-sensing receptor(CaSR)inhibits both actions.The latter has been well documented in vitro but not in vivo.The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo.AIM To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin(CTX)in mice.METHODS CTX was given orally to C57BL/6 mice to induce diarrhea.Calcium and calci-mimetic R568 were used to activate CaSR.To maximize their local intestinal actions,calcium was administered luminally via oral rehydration solution(ORS),whereas R568 was applied serosally using an intraperitoneal route.To verify that their actions resulted from the intestine,effects were also examined on Cre-lox intestine-specific CaSR knockouts.Diarrhea outcome was measured biochemically by monitoring changes in fecal Cl-or clinically by assessing stool consistency and weight loss.RESULTS CTX induced secretory diarrhea,as evidenced by increases in fecal Cl-,stool consistency,and weight loss following CTX exposure,but did not alter CaSR,neither in content nor in function.Accordingly,calcium and R568 were each able to ameliorate diarrhea when applied to diseased intestines.Intestinal CaSR involvement is suggested by gene knockout experiments where the anti-diarrheal actions of R568 were lost in intestinal epithelial CaSR knockouts(villinCre/Casrflox/flox)and neuronal CaSR knockouts(nestinCre/Casrflox/flox).CONCLUSION Treatment of acute secretory diarrheas remains a global challenge.Despite advances in diarrhea research,few have been made in the realm of diarrhea therapeutics.ORS therapy has remained the standard of care,although it does not halt the losses of intestinal fluid and ions caused by pathogens.There is no cost-effective therapeutic for diarrhea.This and other studies suggest that adding calcium to ORS or using calcimimetics to activate intestinal CaSR might represent a novel approach for treating secretory diarrheal diseases.

Relationship between dietary fiber intake and chronic diarrhea in adults

BACKGROUND Dietary fiber is essential for human health and can help reduce the symptoms of constipation.However,the relationship between dietary fiber and diarrhea is,poorly understood.AIM To evaluate the relationship between dietary fiber and chronic diarrhea.METHODS This retrospective study was conducted using data from the United States National Health and Nutrition Examination Survey,conducted between 2005 and 2010.Participants over the age of 20 were included.To measure dietary fiber consumption,two 24-hour meal recall interviews were conducted.The independent relationship between the total amount of dietary fiber and chronic diarrhea was evaluated with multiple logistic regression and interaction analysis.RESULTS Data from 12829 participants were analyzed.Participants without chronic diarrhea consumed more dietary fiber than participants with chronic diarrhea(29.7 vs 28.5,P=0.004).Additionally,in participants with chronic diarrhea,a correlation between sex and dietary fiber intake was present:Women who consume more than 25 g of dietary fiber daily can reduce the occurrence of chronic diarrhea.CONCLUSION Dietary fiber can reduce the occurrence of chronic diarrhea.

Assessment of the triglyceride glucose index in adult patients with chronic diarrhea and constipation

BACKGROUND Accumulating evidence suggests that the gut microbiome is involved in the pathogenesis of insulin resistance(IR).However,the link between two of the most prevalent bowel disorders,chronic diarrhea and constipation,and the triglyceride glucose(TyG)index,a marker of IR,has not yet been investigated.AIM To investigate the potential association between TyG and the incidence of chronic diarrhea and constipation.METHODS This cross-sectional study enrolled 2400 participants from the National Health and Nutrition Examination Survey database from 2009-2010.TyG was used as an exposure variable,with chronic diarrhea and constipation as determined by the Bristol Stool Form Scale used as the outcome variables.A demographic investigation based on TyG quartile subgroups was performed.The application of multivariate logistic regression models and weighted generalized additive models revealed potential correlations between TyG,chronic diarrhea,and constipation.Subgroup analyses were performed to examine the stability of any potential associations.RESULTS In the chosen sample,chronic diarrhea had a prevalence of 8.00%,while chronic constipation had a prevalence of 8.04%.In multiple logistic regression,a more prominent positive association was found between TyG and chronic diarrhea,particularly in model 1(OR=1.45;95%CI:1.17-1.79,P=0.0007)and model 2(OR=1.40;95%CI:1.12-1.76,P=0.0033).No definite association was observed between the TyG levels and chronic constipation.The weighted generalized additive model findings suggested a more substantial positive association with chronic diarrhea when TyG was less than 9.63(OR=1.89;95%CI:1.05-3.41,P=0.0344),and another positive association with chronic constipation when it was greater than 8.2(OR=1.74;95%CI:1.02-2.95,P=0.0415).The results of the subgroup analyses further strengthen the extrapolation of these results to a wide range of populations.CONCLUSION Higher TyG levels were positively associated with abnormal bowel health.

New paradigm of oral rehydration in patients affected by irritable bowel syndrome with chronic diarrhea

Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms.This disease presents with daily abdominal pain for at least 3 months related to defecation and associated with a change in the frequency of bowel movements and the shape of the stool.International surveys about this disease report a global prevalence of about 1.5%.A new amino acid based electrolyte solution has recently been commercialized for oral rehydration in diarrhea.It is composed of water,electrolytes,and five selected amino acids that function as sodium co-transporters without containing glucose.In recent years,some studies explored the effectiveness of the amino acid based electrolyte beverage in oncologic patients with gastrointestinal mucositis,reporting good results.Recently,a prospective study to evaluate the clinical impact of the amino acid based medical beverage was conducted in patients with diarrhea predominant irritable bowel syndrome.The research was based on a real-life methodology minimizing the disruption of the routine care.One hundred patients suffering from irritable bowel syndrome with diarrhea drank a solution based on selected amino acids twice a day for 2 wk.Each enrolled patient completed the study and showed a significant response rate with regard to stool consistency and pain reduction.Based on this data,we can hypothesize that the amino acid based oral rehydration solution could be a valid tool in the treatment of patients affected by irritable bowel syndrome with diarrhea.It is certainly necessary to plan highquality clinical trials comparing glucose based oral solutions and amino acid based solutions in patients with persisting diarrhea.Probably in the near future all oral rehydration solutions will contain amino acids.

Anti-Cancer Agents Associated Diarrhea:Current Status and Prospects

Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.

Clinical Thoughts and Cases of Jianpi Yishen Sechang Decoction Combined with Acupuncture in the Treatment of Functional Diarrhea

Functional diarrhea(FDr)accounts for a relatively high proportion of digestive diseases.It is an infection that is not accompanied by abdominal pain and shows negative results in laboratory tests for bacteria and viruses.The main symptoms are persistent or recurrent discharge of watery and soft stools.The course of the disease is prolonged and recurring,and the treatment cost is higher and greatly affects the patient’s daily life.The incidence rate has a gradual increase in the trend.Its pathogenesis is complex where Western medicine is mostly used in symptomatic drug treatment.The treatment can be fast-acting and effective in relieving diarrhea.However,the long-term use of Western medicine poses a high risk in terms of side effects and a high chance of recurring upon stopping medication.At the same time,some diarrhea patients show the existence of drug-resistant strains of bacteria,and the overall efficacy of the drug is limited.Chinese medicine is mild and able to provide excellent treatment of diarrhea.With its lower price and cost,most families can afford it.Fengliang Tian,director of traditional Chinese medicine,implemented the“needle and medicine”method,which combines medicine and acupuncture,involving the usage of Jianpi Yishen Sechang Decoction and acupuncture in the treatment of functional diarrhea.The method has a low price,fewer side effects,is easy to accept,and can significantly reduce the recurrence rate with high efficacy.The study would like to share the clinical thinking and cases as follows to provide ideas and methods for the treatment of functional diarrhea by traditional Chinese medicine.

Current Research Status of Traditional Chinese Medicine External Treatment for Diarrhea Type Irritable Bowel Syndrome

Irritable bowel syndrome(IBS-D)with diarrhea is a common gastrointestinal functional disease in clinical practice,which seriously affects the quality of life of patients.Cur‐rently,Western medicine has poor therapeutic effects,while traditional Chinese medi‐cine has unique advantages in relieving IBS-D symptoms and preventing recurrence.In recent years,especially with external treatment of traditional Chinese medicine,it has become a new treatment direction in clinical practice and has achieved good therapeutic effects.This article will provide a review of recent research on the treatment of IBS-D using traditional Chinese medicine external treatment methods.

Research on Mechanism and Application of DUAN-NAI-AN on Controlling Weaned Piglet Diarrhea

[ Objective] The study aimed to explore the function mechanism of microbial ecological agent DUAN-NAI-AN on controlling weaned piglet diarrhea. E Method] DUAN-NAI-AN was given to the weaned piglets by oral administration and its effects on diarrhea rate, growth performance, in- testinal microflora, pH values of different parts of the intestine and intestinal mucosal morphology were observed. [ Result] DUAN-NAI-AN could im- prove the growth performance of weaned piglets by increasing the growth rate and phase weight gain, showing as higher livability, average daily gain and daily feed intake as well as lower diarrhea rate with 19.24% decline by contrast to the control. In addition, DUAN-NAI-AN could keep the intestinal mucosal mechanical barrier and normal digestive function by strengthening intestinal resistance and thus enhance the intestinal mucosal im- mune level. It could also decrease the proportion of potential pathogens and their toxicity effects inside the intestine to help the piglets transfer to and then maintain the dynamic balance of intestinal microflora in a very short period, and it also showed a trend of decreasing the pH value of piglet in- testinal contents. [ Conclusion] DUAN-NAI-AN is an effective microbial ecological agent for the control of weaned piglet diarrhea.

Effects of a Self-made Compound Chinese Herbal Medicine Additive on Growth Performance and Occurrence of Diarrhea in Weaned Piglets

In this study,the effects of compound Chinese herbal medicine on growth performance and occurrence of diarrhea in weaned piglets were investigated.A compound Chinese herbal medicine that consisted of Astragalus membranaceus,Codonopsis pilosula,Epimedium sagittatum,massa medicata fermentata,Atractylodes macrocephala,malt,Glycyrrhiza uralensis,Angelica sinensis and Crataegus pinnatifida,was crushed and then passed through a 500-mesh sieve.The obtained powder was added to the basal diet of weaned piglets.A total of 100 healthy crossbred weaned piglets,aging 26±2 days,were selected.They were randomly divided into 5groups（20 piglets/group） in according to principles of similar parity（3-5）,similar body weight and half male and half female.The piglets in the control group were fed with basal diet.For the piglets in the I,II and III groups,0.4%,0.7% and 1.0%of Chinese herbal medicine additive were added to the basal diets,respectively.The basal diet of piglets in the IV group was added with 30 mg/kg of oxytetracycline.The results showed the incidences of diarrhea in I,II and III groups were4.85%,5.14% and 5.63% lower than that of control groups（P〈0.05）.There was no significant difference in incidence of diarrhea between the control and the IV groups.

Development of an One-step Reverse Transcription Loop-mediated Isothermal Amplification Method for Rapid Detection of Bovine Viral Diarrhea Virus

Objective] This study aimed to develop a reverse transcription loop-medi-ated isothermal amplification （RT-LAMP） method for detecting BVDV. [Method] Since gp48 gene of BVDV is among the most conserved regions, a set of four primers was designed to amplify six target sequences at the gp48 gene region for the RT-LAMP assay. The optimization of the RT-LAMP reaction was performed by evaluat-ing reaction temperature and reaction time. [Result] The RT-LAMP aasay was suc-cessful y conducted at 56 ℃ within 40 min under isothermal conditions, and the re-sults could be detected as ladder-like bands using agarose gel electrophoresis. The RT-LAMP assay is highly sensitive and able to detect 3.74 ×100 copies/μl of BVDV RNA, as no cross-reaction was observed with other viruses. [Conclusion] Overal , the newly established RT-LAMP assay indicates the potential application in both clinical diagnosis and field surveil ance of BVDV.