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PloS One 2024Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings,...
Praziquantel-related visual disorders among recipients in mass drug administration campaigns in schistosomiasis endemic settings: Systematic review and meta-analysis protocol.
BACKGROUND
Hundreds of millions of doses of Praziquantel (PZQ) have been administered to persons with and without schistosomiasis living in schistosomiasis endemic settings, through the mass drug administration (MDA) strategy which started in the early 2000s. A recent publication suggested high risk of PZQ-related visual disorders, raising public health concerns. We aim to systematically synthesize evidence on the magnitude of PZQ-related visual disorders.
METHODS
We will search PubMed, Google Scholar, CINAHL, SCOPUS, CENTRAL and LILACS from 1977 (when the first human clinical trials on PZQ started) to 31st May 2024, with no language restrictions. The key search terms will include "Praziquantel", "PZQ", "visual disorder", "adverse events", "side effects", "blurry vision" and "visual impairment" together with alternative terms and synonyms. All the countries endemic for schistosomiasis will be included as search terms. We will also search HINARI, Africa Journals Online, Thesis Databases and Preprint Repositories. Where necessary, we will contact expert researchers working in the field of schistosomiasis, UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR), pharmaceutical industries, country-specific Food and Drug Authorities (FDAs) and the European Medicines Agency databases. We will search Conference Proceedings and reference lists of relevant studies for additional studies. At least two authors will independently select studies, extract data and assess risk of bias in the included studies. Any disagreements or discrepancies will be resolved through discussion between the reviewers. Heterogeneity will be explored graphically, and statistically using the I2-statistic. We will conduct random-effects meta-analysis when heterogeneity is appreciable, and express dichotomous outcomes (visual adverse events including excessive lacrimation, blurry vision and visual impairments) as risk ratio (RR) or Odds Ratio (OR) with their 95% confidence interval (CI). We will perform subgroup analysis to assess the impact of heterogeneity, and sensitivity analyses to test the robustness of the effect estimates. The overall level of evidence will be assessed using GRADE.
EXPECTED OUTCOMES
The present review expects to identify and categorize visual disorders occurring after administration of PZQ, alone or in combination with other drugs. By synthesizing the data from multiple studies, the review aims to present a quantitative assessment of the risk or odds of experiencing a visual disorder in different populations after ingesting PZQ. The review will also generate insights into whether PZQ in combination with other drugs are associated with increased odds of visual disorders and whether the occurrence of visual disorders correlates with dosage or treatment duration. Policymakers, public health experts and stakeholders could rely on the review findings to deliver context-sensitive preventive chemotherapy programs by adjusting drug combinations or dosing schedules to reduce risk of visual adverse effects in populations treated with PZQ. The review aims to identify gaps in the current evidence regarding visual disorders following PZQ administration in schistosomiasis endemic settings which can serve as the basis for future research on important but unanswered questions.
DISSEMINATION AND PROTOCOL REGISTRATION
The findings of this study will be disseminated through stakeholder forums, conferences, and peer-review publications. The review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO)- CRD42023417963.
Topics: Humans; Schistosomiasis; Praziquantel; Vision Disorders; Systematic Reviews as Topic; Mass Drug Administration; Meta-Analysis as Topic; Endemic Diseases; Anthelmintics
PubMed: 38758736
DOI: 10.1371/journal.pone.0300384 -
Allergologie Select 2024None.
None.
PubMed: 38756207
DOI: 10.5414/ALX02444E -
Experimental Biology and Medicine... 2024Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal...
Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal sensitivity. The impact of diabetes on the lacrimal functional unit (LFU) and the structures responsible for maintaining tear homeostasis, is not completely known. It has been shown that the Opioid Growth Factor Receptor (OGFr), and its ligand, Opioid Growth Factor (OGF), is dysregulated in the ocular surface of diabetic rats leading to overproduction of the inhibitory growth peptide OGF. The opioid antagonist naltrexone hydrochloride (NTX) blocks the OGF-OGFr pathway, and complete blockade following systemic or topical treatment with NTX restores the rate of re-epithelialization of corneal epithelial wounds, normalizes corneal sensitivity, and reverses dry eye in diabetic animal models. These effects occur rapidly and within days of initiating treatment. The present study was designed to understand mechanisms related to the fast reversal (<5 days) of dry eye by NTX in type 1 diabetes (T1D) by investigating dysregulation of the LFU. The approach involved examination of the morphology of the LFU before and after NTX treatment. Male and female adult Sprague-Dawley rats were rendered hyperglycemic with streptozotocin, and after 6 weeks rats were considered to be a T1D model. Rats received topical NTX twice daily to one eye for 10 days. During the period of treatment, tear production and corneal sensitivity were recorded. On day 11, animals were euthanized and orbital tissues including conjunctiva, eyelids, and lacrimal glands, were removed and processed for histologic examination including immunohistochemistry. Male and female T1D rats had significantly decreased tear production and corneal insensitivity, significantly decreased number and size of lacrimal gland acini, decreased expression of aquaporin-5 (AQP5) protein and decreased goblet cell size. Thus, 10 days of NTX treatment restored tear production and corneal sensitivity to normal values, increased AQP5 expression, and restored the surface area of goblet cells to normal. NTX had no effect on the number of lacrimal gland acini or the number of conjunctival goblet cells. In summary, blockade of the OGF-OGFr pathway with NTX reversed corneal and lacrimal gland complications and restored some components of tear homeostasis confirming the efficacy of topical NTX as a treatment for ocular defects in diabetes.
Topics: Animals; Lacrimal Apparatus; Tears; Naltrexone; Rats, Sprague-Dawley; Male; Diabetes Mellitus, Experimental; Rats; Aquaporin 5; Administration, Topical; Dry Eye Syndromes
PubMed: 38756167
DOI: 10.3389/ebm.2024.10175 -
Acta Otorhinolaryngologica Italica :... May 2024
Review
Topics: Humans; Eye Neoplasms; Endoscopy; Lacrimal Apparatus; Lacrimal Apparatus Diseases
PubMed: 38745518
DOI: 10.14639/0392-100X-suppl.1-44-2024-N2966 -
Radiology Case Reports Aug 2024Sarcoidosis, a multifaceted granulomatous disease primarily affecting the lungs, occasionally presents in atypical locations. Lacrimal gland involvement, though rare,...
Sarcoidosis, a multifaceted granulomatous disease primarily affecting the lungs, occasionally presents in atypical locations. Lacrimal gland involvement, though rare, poses distinct diagnostic challenges. This case report details a 52-year-old female with bilateral lacrimal gland swelling initially suggestive of metastatic tumor due to a history of breast cancer. Subsequent investigations, including CT and MRI, unveiled pulmonary sarcoidosis. Discussion emphasizes the diverse ocular manifestations of sarcoidosis, with lacrimal gland participation potentially indicating early stages. Diagnostic complexities involve differentiation from other lacrimal pathologies, including neoplasms, lymphoproliferative disorders, Sjögren's syndrome, Wegener's granulomatosis, tuberculosis, and IgG4-related disease. In summary, while lacrimal gland involvement in sarcoidosis is infrequent, it should be considered in orbital masses, necessitating a comprehensive approach for accurate diagnostic orientation in such cases.
PubMed: 38737175
DOI: 10.1016/j.radcr.2024.04.010 -
International Journal of Molecular... May 2024Sjögren's Disease (SjD) is an autoimmune disease of the exocrine tissues. Etiological events result in the loss of epithelial homeostasis alongside extracellular matrix... (Review)
Review
Sjögren's Disease (SjD) is an autoimmune disease of the exocrine tissues. Etiological events result in the loss of epithelial homeostasis alongside extracellular matrix (ECM) destruction within the salivary and lacrimal glands, followed by immune cell infiltration. In this review, we have assessed the current understanding of epithelial-mesenchymal transition (EMT)-associated changes within the salivary epithelium potentially involved in salivary dysfunction and SjD pathogenesis. We performed a PubMed literature review pertaining to the determination of pathogenic events that lead to EMT-related epithelial dysfunction and signaling in SjD. Molecular patterns of epithelial dysfunction in SjD salivary glands share commonalities with EMT mediating wound healing. Pathological changes altering salivary gland integrity and function may precede direct immune involvement while perpetuating MMP9-mediated ECM destruction, inflammatory mediator expression, and eventual immune cell infiltration. Dysregulation of EMT-associated factors is present in the salivary epithelium of SjD and may be significant in initiating and perpetuating the disease. In this review, we further highlight the gap regarding mechanisms that drive epithelial dysfunction in salivary glands in the early or subclinical pre-lymphocytic infiltration stages of SjD.
Topics: Humans; Sjogren's Syndrome; Epithelial-Mesenchymal Transition; Salivary Glands; Animals; Epithelium; Epithelial Cells; Signal Transduction; Extracellular Matrix
PubMed: 38732189
DOI: 10.3390/ijms25094973 -
Contact Lens & Anterior Eye : the... May 2024Diabetes mellitus (DM) can be defined as a metabolic disorder that results from either the inability of insulin to perform its normal functions or decreased insulin...
BACKGROUND
Diabetes mellitus (DM) can be defined as a metabolic disorder that results from either the inability of insulin to perform its normal functions or decreased insulin secretion. Dry eye disease is a complex ailment of the tear film resulting in discomfort characterised by pain, a feeling of heavy eyes, grittiness, burning, dryness, itchiness, foreign body sensation, and visual disturbances. Patients with chronic conditions, i.e. DM, are more susceptible to developing dry eye due to various complications that may arise, such as, peripheral neuropathy, inflammatory alterations and reduced lacrimal gland function.
AIM
To identify the prevalence of dry eye syndrome in paediatric patients diagnosed with Diabetes Mellitus (Type 1/2).
METHOD
37 children with diabetes and 40 healthy, age group matched controls were enrolled in this study. Participants underwent a complete dry eye assessment in the following order: Ocular Surface Disease Index (OSDI) and McMonnies questionnaire, meibomian gland evaluation using white light, Tear Break-up Test (TBUT), Phenol Red Thread (PRT) test and Tear film Osmolarity test. Duration of diabetes was used as the parameter.
RESULTS
The incidence of dry eye syndrome was found to be higher among diabetics, with 15 (40.5 %) from the diabetic population compared to 4 (10.0 %) from the control group. TBUT and PRT test values were significantly reduced in children with diabetes (p < 0.001). TFO values were higher in the diabetics. No statistically significant differences were found the questionnaire scores, of the two groups, however the diabetic group appeared to be less symptomatic.
CONCLUSION
Dry eye is more common in the diabetic paediatric population. TBUT and PRT results were found to be lower in diabetics. Results showed a strong correlation between duration of diabetes and TBUT values. Healthcare practitioners, working with children diagnosed with diabetes, should raise awareness as well as encourage early dry eye screening and intervention.
CLINICAL SIGNIFICANCE
Due to the steady increase in the number of children and adolescents with diabetes, the characteristics and prevalence of dry eye syndrome in this population has become more valuable.
PubMed: 38724426
DOI: 10.1016/j.clae.2024.102175 -
International Journal of Ophthalmology 2024To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats.
AIM
To investigate the underlying mechanism of dry environment (autumn dryness) affecting the lacrimal glands in rats.
METHODS
Twenty Sprague-Dawley rats were randomly divided into two groups. The rats were fed in specific pathogen free environment as the control group (=10), and the rats fed in dry environment as the dryness group (=10). After 24d, lacrimal glands were collected from the rats. The tissues morphology was observed by hematoxylin-eosin (HE) staining. Tandem mass tags (TMT) quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups, then bioinformatics analysis was performed. Further, the immunohistochemical (IHC) method was used to verify the target proteins.
RESULTS
In dryness group, the lacrimal glands lobule atrophied, the glandular cavities enlarged, the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed. The proteomics exhibited that a total of 195 up-regulated and 236 down-regulated differential expressed proteins screened from the lacrimal glands of rats. It was indicated that the biological processes (BP) of differential expressed proteins mainly included cell processes and single BP. The cellular compositions of differential expressed proteins mainly located in cells, organelles. The molecular functions of differential expressed proteins mainly included binding, catalytic activity. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the differential expressed proteins mainly involved lysosome, complement and coagulation cascade, and ribosome pathway. The IHC result verified that the up-regulated expression proteins of Protein S100A9 (S100A9), Annexin A1 (Anxa1), and Clusterin (Clu) in lacrimal glands of rats in dryness group were higher than control group.
CONCLUSION
The up-regulated expression proteins of S100A9, Anxa1, and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment. This study provides clues of dry environments causing eye-related diseases for further studies.
PubMed: 38721521
DOI: 10.18240/ijo.2024.03.04 -
Pediatric Neurology Apr 2024The pediatric migraine phenotype may exhibit differences to adults, leading to diagnostic challenges. We aimed to perform a cross-sectional systematic study to...
BACKGROUND
The pediatric migraine phenotype may exhibit differences to adults, leading to diagnostic challenges. We aimed to perform a cross-sectional systematic study to characterize the extended phenotype of pediatric migraine.
METHODS
New migraine patients presenting to the Children's Headache Clinic were included (n = 105). Data were collected via a detailed symptom questionnaire at the first clinical encounter and were analyzed using descriptive statistics, Cohen kappa (k), Spearman correlation (ρ), and Poisson and binomial logistic regression models within SPSS.
RESULTS
Patients were 65% female and aged five to 17 years (median 14, interquartile range [IQR] 11 to 15), with a mean disease duration of 4.7 years (S.D. 2.8). Monthly headache frequency was 1 to 30 days (median 30, IQR 12 to 30). Attack duration varied between 2 and 168 hours (median 12, IQR 5 to 72). The majority (81%) experienced bilateral headache. Premonitory symptoms (PS) were reported by 93% (range 0 to 7; mood change and tiredness most commonly), cranial autonomic symptoms (CAS) by 58% (range 0 to 6; pallor and lacrimation most commonly), and premonitory CAS by 23%. Vertigo (53%) and allodynia (16%) were present. The laterality of headache and CAS showed agreement (k = 0.5, P < 0.001). For every year of disease duration, 1.07 times more PS were reported (95% confidence interval [CI] 1.03 to 1.12, P < 0.001). The number of CAS (odds ratio 2.13, 95% CI 1.2 to 3.8, P = 0.01) significantly predicted allodynia.
CONCLUSIONS
Children display a more enriched PS phenotype with disease chronicity. CAS and allodynia may be markers of central sensitization with shared neurobiological mechanisms in the absence of peripheral nociceptor activation.
PubMed: 38718550
DOI: 10.1016/j.pediatrneurol.2024.03.026 -
Integrative Medicine Research Jun 2024Tagetes erecta Linn, popularly known as Marigold, has various pharmacological effects. It is used as a dietary supplement, especially for the posterior segment of the...
BACKGROUND
Tagetes erecta Linn, popularly known as Marigold, has various pharmacological effects. It is used as a dietary supplement, especially for the posterior segment of the eye. However, the effect of T. erecta Linn on ocular disorders is still unknown. The purpose of this study was to investigate the effect of oral administration of ethanol extract of Linn flower (TE) for dry eye syndrome (DED) in a murine model.
METHODS
Twenty-four mice were subjected to desiccation stress (DS) to induce DED and subcutaneous injection of scopolamine hydrobromide was administered 4 times a day for 21 days. TE and cyclosporine A (CsA) were administered for an additional 14 days under DS conditions. Mice were randomly divided into four groups: control, TE200, TE400, and CsA. Changes in tear production and corneal fluorescein staining were measured at baseline, after 7 days of DS, and after treatment for 7 and 14 days.
RESULTS
DS significantly decreased tear production and increased corneal fluorescein score; the parameters were significantly reversed in the TE400 (oral administration of 400 mg TE/kg body weight) group. TE markedly improved DS-induced changes including corneal epithelial detachment and lacrimal gland inflammation. The anti-inflammatory effect of TE 400 supplementation was similar to that of CsA.
CONCLUSIONS
Our findings suggest that oral administration of TE may protect against DS-induced DED stabilization of the tear film and suppression of inflammation. This study provides an experimental basis for further studies on the potential clinical use of TE in preventing DED.
PubMed: 38716164
DOI: 10.1016/j.imr.2024.101038