Paediatric pulmonary actinomycosis: A forgotten disease.

Actinomycosis is a rare, indolent and invasive infection caused by Actinomyces species. Actinomycosis develops when there is disruption of the mucosal barrier, and invasion and systemic spread of the organism, which can lead to endogenous infection affecting numerous organs. It is known to spread in tissue through fascial planes and most often involves the cervicofacial (55%), abdominopelvic (20%) and thoracic (15%) soft tissue. Pulmonary actinomycosis is rare in patients under the age of five years, with the median reported age in the fifth decade. Clinical findings include chest wall mass (49%), cough (40%), pain (back, chest, shoulders) (36%), weight loss (19%), fever (19%), Draining sinuses (15%) and hemoptysis (9%). Chest x-ray findings in pulmonary actinomycosis are mostly nonspecific and can overlap with pulmonary tuberculosis, foreign body aspiration and malignancy. Endobronchial tissue aggregates may show sulphur granules, with yellow to white conglomerate areas of gram positive Actinomyces. Removal or biopsy of these large endobronchial masses must be done with care, because of the risk of bleeding and large airway obstruction. The cytology on bronchoalveolar lavage fluid may show Periodic acid-Schiff (PAS) positive stain, ZN negative and Gram-positive filamentous bacilli which is morphologically suggestive of Actinomycosis. Actinomyces spp is highly susceptible to beta lactam antibiotics, penicillin G, and amoxicillin. A minimum of 3-6 months is needed but up to 20 months of treatment may be needed. Early diagnosis and correct treatment can lead to a good prognosis with a low mortality.

Negatively Charged Sulfur Quantum Dots for Treatment of Drug-Resistant Pathogenic Bacterial Infections.

Drug-resistant pathogenic bacteria as a worldwide health threat calls for valid antimicrobial agents and tactics in clinical practice. Positively charged materials usually achieve antibacteria through binding and disrupting bacterial membranes via electrostatic interaction, however, they also usually cause hemolysis and cytotoxicity. Herein, we engineered negatively charged sulfur quantum dots (SQDs) as an efficient broad-spectrum antibiotic to kill drug-resistant bacteria in vitro and in vivo. The SQDs can destroy the bacterial membrane system and affect their metabolism due to the intrinsic antibacterial activity of elemental sulfur and catalytic generation of reactive oxygen species, which exhibit effective therapeutic effect on subcutaneously implanted infection model induced by representative pathogenic Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Plus, the negatively charged surface makes the SQDs have excellent hemocompatibility and low toxicity, which all highlight the critical prospect of the SQDs as a potent biocompatible antibacterial agent in clinical infection therapy.

Co-administration of sodium hydrosulfide and tadalafil modulates hypoxia and oxidative stress on bladder dysfunction in a rat model of bladder outlet obstruction.

PURPOSE: This study aimed to assess the possible healing effect of combination treatment with a hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS) plus tadalafil on partial bladder outlet obstruction (PBOO)-induced bladder dysfunction. MATERIALS AND METHODS: A total of 75 male Sprague-Dawley rats aged 10-wk and 300-350g were divided into five groups; control; PBOO; PBOO+NaHS (5.6mg/kg/day, i.p., 6-wk); PBOO+tadalafil (2mg/kg/day, oral, 6-wk) and PBOO+NaHS+tadalafil. PBOO was created by partial urethral ligation. 6 weeks after obstruction, the in vitro contractile responses of the detrusor muscle and Western blotting, H2S and malondialdehyde assay were performed in bladder tissues. RESULTS: There was an increase in bladder weight(p<0.001) and a decrease in contractile responses to KCL(p<0.001), carbachol(p<0.01), electrical field stimulation(p<0.05) and ATP (p<0.001) in the detrusor smooth muscle of obstructed rats which was normalized after the combination treatment. Cystathionine γ-lyase and cystathionine ß-synthase, and nuclear factor kappa B protein levels did not significantly differ among groups. The obstruction induced decrement in 3-mercaptopyruvate sulfur transferase protein expression(p<0.001) and H2S levels(p<0.01) as well as increment in protein expressions of neuronal nitric oxide synthase (NO, p<0.001), endothelial NOS (p<0.05), inducible NOS(p<0.001), hypoxia-inducible factor 1-alpha (p<0.01), and malondialdehyde levels (p<0.01), when combined treatment entirely normalized. CONCLUSIONS: Combination therapy has beneficial effects on bladder dysfunction via regulating both H2S and nitric oxide pathways as well as downregulation of oxidative stress and hypoxia. The synergistic effect of H2S and nitric oxide is likely to modulate bladder function, which supports the combined therapy for enhancing clinical outcomes in men with BPH/LUTS.

Sulfur Induces Resistance against Canker Caused by Pseudomonas syringae pv. actinidae via Phenolic Components Increase and Morphological Structure Modification in the Kiwifruit Stems.

Bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) has led to considerable losses in all major kiwifruit-growing areas. There are no commercial products in the market to effectively control this disease. Therefore, the defense resistance of host plants is a prospective option. In our previous study, sulfur could improve the resistance of kiwifruit to Psa infection. However, the mechanisms of inducing resistance remain largely unclear. In this study, disease severity and protection efficiency were tested after applying sulfur, with different concentrations in the field. The results indicated that sulfur could reduce the disease index by 30.26 and 31.6 and recorded high protection efficiency of 76.67% and 77.00% after one and two years, respectively, when the concentration of induction treatments was 2.0 kg/m3. Ultrastructural changes in kiwifruit stems after induction were demonstrated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and the activities of phenylalanine ammonia-lyase (PAL), peroxidase (POD) and polyphenol oxidase (PPO), and the accumulation of lignin were determined by biochemical analyses. Our results showed that the morphological characteristics of trichomes and lenticels of kiwifruit stem were in the best defensive state respectively when the sulfur concentration was 3.0 kg/m3 and 1.5 kg/m3. Meanwhile, in the range of 0.5 to 2.0 kg/m3, the sulfur could promote the chloroplast and mitochondria of kiwifruit stems infected with Psa to gradually return to health status, increasing the thickness of the cell wall. In addition, sulfur increased the activities of PAL, POD and PPO, and promoted the accumulation of lignin in kiwifruit stems. Moreover, the sulfur protection efficiency was positively correlated with PPO activity (p < 0.05) and lignin content (p < 0.01), which revealed that the synergistic effect of protective enzyme activity and the phenolic metabolism pathway was the physiological effect of sulfur-induced kiwifruit resistance to Psa. This evidence highlights the importance of lignin content in kiwifruit stems as a defense mechanism in sulfur-induced resistance. These results suggest that sulfur enhances kiwifruit canker resistance via an increase in phenolic components and morphology structure modification in the kiwifruit stems. Therefore, this study could provide insights into sulfur to control kiwifruit canker caused by Psa.

Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc and fruit acid (alpha-hydroxy acid) for acne.

BACKGROUND: Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the topical acne treatments azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha-hydroxy acid is unclear. OBJECTIVES: To assess the effects of topical treatments (azelaic acid, salicylic acid, nicotinamide, zinc, alpha-hydroxy acid, and sulphur) for acne. SEARCH METHODS: We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers. SELECTION CRITERIA: Clinical randomised controlled trials of the six topical treatments compared with other topical treatments, placebo, or no treatment in people with acne. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Key outcomes included participants' global self-assessment of acne improvement (PGA), withdrawal for any reason, minor adverse events (assessed as total number of participants who experienced at least one minor adverse event), and quality of life. MAIN RESULTS: We included 49 trials (3880 reported participants) set in clinics, hospitals, research centres, and university settings in Europe, Asia, and the USA. The vast majority of participants had mild to moderate acne, were aged between 12 to 30 years (range: 10 to 45 years), and were female. Treatment lasted over eight weeks in 59% of the studies. Study duration ranged from three months to three years. We assessed 26 studies as being at high risk of bias in at least one domain, but most domains were at low or unclear risk of bias. We grouped outcome assessment into short-term (less than or equal to 4 weeks), medium-term (from 5 to 8 weeks), and long-term treatment (more than 8 weeks). The following results were measured at the end of treatment, which was mainly long-term for the PGA outcome and mixed length (medium-term mainly) for minor adverse events. Azelaic acid In terms of treatment response (PGA), azelaic acid is probably less effective than benzoyl peroxide (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.95; 1 study, 351 participants), but there is probably little or no difference when comparing azelaic acid to tretinoin (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 289 participants) (both moderate-quality evidence). There may be little or no difference in PGA when comparing azelaic acid to clindamycin (RR 1.13, 95% CI 0.92 to 1.38; 1 study, 229 participants; low-quality evidence), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). Low-quality evidence indicates there may be no differences in rates of withdrawal for any reason when comparing azelaic acid with benzoyl peroxide (RR 0.88, 95% CI 0.60 to 1.29; 1 study, 351 participants), clindamycin (RR 1.30, 95% CI 0.48 to 3.56; 2 studies, 329 participants), or tretinoin (RR 0.66, 95% CI 0.29 to 1.47; 2 studies, 309 participants), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). In terms of total minor adverse events, we are uncertain if there is a difference between azelaic acid compared to adapalene (1 study; 55 participants) or benzoyl peroxide (1 study, 30 participants) (both very low-quality evidence). There may be no difference when comparing azelaic acid to clindamycin (RR 1.50, 95% CI 0.67 to 3.35; 1 study, 100 participants; low-quality evidence). Total minor adverse events were not reported in the comparison of azelaic acid versus tretinoin, but individual application site reactions were reported, such as scaling. Salicylic acid For PGA, there may be little or no difference between salicylic acid and tretinoin (RR 1.00, 95% CI 0.92 to 1.09; 1 study, 46 participants; low-quality evidence); we are not certain whether there is a difference between salicylic acid and pyruvic acid (1 study, 86 participants; very low-quality evidence); and PGA was not measured in the comparison of salicylic acid versus benzoyl peroxide. There may be no difference between groups in withdrawals when comparing salicylic acid and pyruvic acid (RR 0.89, 95% CI 0.53 to 1.50; 1 study, 86 participants); when salicylic acid was compared to tretinoin, neither group had withdrawals (both based on low-quality evidence (2 studies, 74 participants)). We are uncertain whether there is a difference in withdrawals between salicylic acid and benzoyl peroxide (1 study, 41 participants; very low-quality evidence). For total minor adverse events, we are uncertain if there is any difference between salicylic acid and benzoyl peroxide (1 study, 41 participants) or tretinoin (2 studies, 74 participants) (both very low-quality evidence). This outcome was not reported for salicylic acid versus pyruvic acid, but individual application site reactions were reported, such as scaling and redness. Nicotinamide Four studies evaluated nicotinamide against clindamycin or erythromycin, but none measured PGA. Low-quality evidence showed there may be no difference in withdrawals between nicotinamide and clindamycin (RR 1.12, 95% CI 0.49 to 2.60; 3 studies, 216 participants) or erythromycin (RR 1.40, 95% CI 0.46 to 4.22; 1 study, 158 participants), or in total minor adverse events between nicotinamide and clindamycin (RR 1.20, 95% CI 0.73 to 1.99; 3 studies, 216 participants; low-quality evidence). Total minor adverse events were not reported in the nicotinamide versus erythromycin comparison. Alpha-hydroxy (fruit) acid There may be no difference in PGA when comparing glycolic acid peel to salicylic-mandelic acid peel (RR 1.06, 95% CI 0.88 to 1.26; 1 study, 40 participants; low-quality evidence), and we are uncertain if there is a difference in total minor adverse events due to very low-quality evidence (1 study, 44 participants). Neither group had withdrawals (2 studies, 84 participants; low-quality evidence). AUTHORS' CONCLUSIONS: Compared to benzoyl peroxide, azelaic acid probably leads to a worse treatment response, measured using PGA. When compared to tretinoin, azelaic acid probably makes little or no difference to treatment response. For other comparisons and outcomes the quality of evidence was low or very low. Risk of bias and imprecision limit our confidence in the evidence. We encourage the comparison of more methodologically robust head-to-head trials against commonly used active drugs.

Efficacy and safety of antiscabietic agents: A systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Many drugs have been used to treat scabies, but it is unclear which of them is the most efficacious. OBJECTIVE: To evaluate the comparative efficacy and safety of antiscabietic agents. METHODS: A systematic review of randomized controlled trials was conducted. Direct and network meta-analyses were applied to 13 antiscabietic agents on 3 outcomes (cure, persistent itching, and adverse events). Their probability of having highest efficacy and safety was estimated and ranked. RESULTS: A network meta-analysis of 52 trials including 9917 patients indicated that permethrin (the reference treatment) had a significantly higher cure rate than sulfur, malathion, lindane, crotamiton, and benzyl benzoate. Combination permethrin plus oral ivermectin had a nonsignificantly higher cure rate than permethrin. Combination permethrin plus oral ivermectin was ranked highest in terms of cure, topical ivermectin in terms of persistent itching, and synergized pyrethrins in terms of adverse events. On the basis of clustered ranking, permethrin, oral ivermectin, and synergized pyrethrins seemed to retain balance between cure and adverse events. LIMITATIONS: There are small numbers of trials and patients in some comparisons and a high risk of bias in some trials. CONCLUSION: There is no 1 treatment that ranked highest in all aspects. Physicians should consider the drug's efficacy and safety profiles, along with ease of administration.

Effect of Homeopathic Medicines and a Nosode on Larvae of Cochliomyia hominivorax (Diptera: Calliphoridae).

BACKGROUND: Cochliomyia hominivorax is the major fly causing primary myiasis in livestock animals in Brazil; its larvae develop in the host's living tissues, causing mutilations, which can even lead to death. In conventional treatments of myiasis, chemo-synthetic insecticides have been employed directly on larvae present in the wounds. Homeopathy may represent a healthy and sustainable alternative both to prevent and to treat myiasis in animals and humans. The current study evaluated how the emergence of adult insects is affected by the use of the homeopathic medicines Sulfur 12cH and Pyrogenium 12cH, and the nosode produced from C. hominivorax larvae at potencies 8cH and 12cH, on third-stage larvae of a C. hominivorax colony. MATERIALS AND METHODS: The homeopathic medicines and the nosodes were produced according to the Brazilian Homeopathic Pharmacopoeia. Control groups were distilled water, alcohol, no substance, and the organophosphate insecticide trichlorfon. For each group, 10 replicates were performed. Emergence rate of adult insects was evaluated by descriptive statistics followed by analysis of variance. Homogeneity of variances was verified by F-test and group means were compared with Tukey's test. RESULTS: Mortality rates in control groups were 2.7% for 30% (v/v) alcohol, 4.3% for distilled water, 3.2% for no substance (p > 0.05). In the trichlorfon group, the mortality rate of larvae was 90.8%. For Sulfur 12cH, the mortality of larvae was 94.6%, and for Pyrogenium 12cH it was 98.6%. The latter three means were not statistically different from each other or from the mean found for the trichlorfon group. The mortality rates of larvae were 61.3% and 66.6% for nosode C. hominivorax 8cH and 12cH, respectively (p > 0.05). CONCLUSIONS: Results suggest that homeopathy could be used therapeutically to prevent and treat animals and humans with myiasis caused by C. hominivorax.

Effects of sulfur bath on hip osteoarthritis: a randomized, controlled, single-blind, follow-up trial: a pilot study.

The effects of balneotherapy were evaluated in patients with osteoarthritis of the hip. This randomized, controlled, investigator-blinded study enrolled outpatients with hip osteoarthritis according to ACR criteria. In addition to home exercise therapy, one patient group received balneotherapy for 3 weeks on 15 occasions. The mineral water used in this study is one of the mineral waters with the highest sulfide ion content (13.2 mg/L) in Hungary. The control group received exercise therapy alone. The WOMAC Likert 3.1 index and the EQ-5D quality of life self-administered questionnaire were completed three times during the study: prior to first treatment, at the end of the 3-week treatment course, and 12 weeks later. The main endpoint was achievement of Minimal Clinically Important Improvement (MCII) at 12 weeks, defined as ≥7.9 points in a normalized WOMAC function score. The intention to treat analysis included 20 controls and 21 balneotherapy patients. At 12 weeks, 17 (81 %) balneotherapy group patients had Minimal Clinically Important Improvement and 6 (30 %) of controls (p = 0.001). Comparing the results of the two groups at the end of treatment, there was a significant difference in the WOMAC stiffness score only, whereas after 12 weeks, the WOMAC pain, stiffness, function, and total scores also showed a significant difference in favor of the balneotherapy group. The difference between the two groups was significant after 12 weeks in point of EQVAS score, too. The results of our study suggest that the combination of balneotherapy and exercise therapy achieves more sustained improvement of joint function and decreases in pain than exercise therapy alone.

Reactivating PTEN to impair glioma stem cells by inhibiting cytosolic iron-sulfur assembly.

Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, the function and regulation of PTEN in PTEN-intact GSCs are unknown. Here, we found that PTEN directly interacted with MMS19 and competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery in differentiated glioma cells. PTEN was specifically succinated at cysteine (C) 211 in GSCs compared with matched differentiated glioma cells. Isotope tracing coupled with mass spectrometry analysis confirmed that fumarate, generated by adenylosuccinate lyase (ADSL) in the de novo purine synthesis pathway that is highly activated in GSCs, promoted PTEN C211 succination. This modification abrogated the interaction between PTEN and MMS19, reactivating the CIA machinery pathway in GSCs. Functionally, inhibiting PTEN C211 succination by reexpressing a PTEN C211S mutant, depleting ADSL by shRNAs, or consuming fumarate by the US Food and Drug Administration-approved prescription drug N-acetylcysteine (NAC) impaired GSC maintenance. Reexpressing PTEN C211S or treating with NAC sensitized GSC-derived brain tumors to temozolomide and irradiation, the standard-of-care treatments for patients with glioblastoma, by slowing CIA machinery-mediated DNA damage repair. These findings reveal an immediately practicable strategy to target GSCs to treat glioblastoma by combination therapy with repurposed NAC.

[Sulfur-fumigation, maintenance method of Chinese herbal medicine-discard or inheritance].

Sulfur-fumigation processing technology is an ancient maintenance method, which plays a certain role in storage and preservation for Chinese herbal medicine. But in recent years, with the further explanation of sulfur-fumigation processing mechanism and more attention to the safety of drugs, such traditional maintenance method of Chinese herbal medicine is now being questioned by more and more people. The authors think we should have selective inheritance rather than abslute discard to this ancient processing technology after reviewing the literatures published in recent 20 years, and some suggestions are also put forward, which can supply some references for related drug supervision departments.

Broad-Spectrum Anti-Flavivirus Activity and Chemistry of Compounds Containing Sulfur and Oxygen Chalcogens.

Sulfur and oxygen containing-compounds are a relevant class of derivatives that is constantly growing due to their wide range of pharmacological activity, including the antiviral one. As proof of this, there are several FDA approved antiviral compounds having sulfur and oxygen in their structures. Among RNA viruses, the flavivirus genus (e.g. Dengue, West Nile, Yellow Fever and Zika viruses) holds a relevant place within zoonotic pathogens and thus flavivirus infections are considered a growing risk for the public health. As a consequence, the drug discovery process aimed at identify new anti- flavivirus agents is of great relevance and will help to find effective therapies not available yet. One of the most alarming features of flaviviruses is their ability to co-infect the host, thus aggravating the symptoms of the disease. Therefore, finding compounds endowed with a broad-spectrum anti-flavivirus activity is now becoming a pressing need. In this review, we describe the most promising compounds having both sulfur and oxygen in their structures characterized by a broad-spectrum activity against different flaviviruses. Furthermore, the synthetic procedures applied for the preparation of the described derivatives are also reported. Readers can be inspired by the contents of this review to design and synthesize more effective anti-flavivirus agents as well as to select viral or host targets to achieve an antiviral activity as broadly as possible.

Bifunctional cysteine gold nanoclusters for ß-amyloid fibril inhibition and fluorescence imaging: a distinctive approach to manage Alzheimer's disease.

Alzheimer's disease (AD) is a progressive complex neurodegenerative disorder affecting millions of individuals worldwide. Currently, there is no effective treatment for AD. AD is characterized by the deposition of amyloid plaques/fibrils. One major strategy for managing this disease is by slowing the progression of AD using different drugs which could potentially limit free-radical formation, oxidative stress and lipid peroxidation and promote the survival of neurons exposed to ß-amyloid. Inhibition of amyloid fibrillization and clearance of amyloid plaques/fibrils are essential for the prevention and treatment of AD. The thiophilic interaction between the side chain of an aromatic residue in a polypeptide and a sulphur atom of the compound can effectively inhibit amyloid fibril formation. In this work, we have synthesized cysteine-capped gold nanoclusters (Cy-AuNCs) which exhibit inherent red emission and can disintegrate amyloid fibrils through the aforementioned thiophilic interactions. Herein, we also used molecular docking to study the thiophilic interactions between the sulphur atom of Cy-AuNCs and the aromatic rings of the protein. Finally, the gold cluster was functionalized with a brain targeting molecule, Levodopa (AuCs-LD), to specifically target the brain and to facilitate passage through the blood brain barrier (BBB). Both Cy-AuNCs and AuCs-LD showed good biocompatibility and the inherent fluorescence properties of nanoclusters enabled real time imaging. The efficacy of the nanoclusters to disintegrate amyloid fibrils and their ability to cross the BBB were demonstrated both in vitro and in vivo in the BBB model and the AD animal model respectively. Our results imply that nanoparticle-based artificial molecular chaperones may offer a promising therapeutic approach for AD.

Housing and dustbathing effects on northern fowl mites (Ornithonyssus sylviarum) and chicken body lice (Menacanthus stramineus) on hens.

Hen housing (cage or cage-free) did not impact overall abundances of northern fowl mites, Ornithonyssus sylviarum (Canestrini & Fanzago) (Acari: Macronyssidae), or chicken body lice, Menacanthus stramineus (Nitzsch) (Phthiraptera: Menoponidae). Cage-free hens received a dustbox with sand plus diatomaceous earth (DE), kaolin clay or sulphur. Weekly use varied from none to 100% of hens; 73% of hens used the dustbox at least once. Ectoparasite populations on dustbathing hens (users) were compared with those on non-user cage-free and caged hens. All materials reduced ectoparasites on user hens by 80-100% after 1 week of dustbox use. Diatomaceous earth and kaolin failed to reduce ectoparasites on non-user hens, and ectoparasites on user hens recovered after dustbox removal. A sulphur dustbox eliminated mites from all hens (including non-users) within 2-4 weeks. Residual sulphur controlled mites until the end of the experiment (up to 9 weeks), even after the dustbox was removed. Louse populations on hens using the sulphur dustbox were reduced in 1-2 weeks. Residual sulphur effects were less evident in lice, but the use of a sulphur dustbox by a higher proportion of hens extended louse control to all hens. This is the first experimental study to show that bird dustbathing in naturally and widely available dust materials (particularly kaolin) can suppress ectoparasites and thus the behaviour is probably adaptive.

Treatment of scabies using 8% and 10% topical sulfur ointment in different regimens of application.

BACKGROUND: Many therapeutic modalities for scabies were available, topical sulfur ointment is a cost-effective and safe therapeutic agent. It is often applied for the whole body for three successive days. OBJECTIVE: To evaluate their therapeutic regimen of 8% and 10% topical precipitated sulfur in petrolatum ointment for single day, three successive nights or three successive days in management of scabies. PATIENTS AND METHODS: This single-blinded, comparative study was conducted in the Department of Dermatology-Baghdad Teaching Hospital from April 2008 through October 2009. A total of 97 patients with scabies were enrolled in this study. The diagnosis was established on clinical basis. The patients treated with 8% and 10% topical sulfur in petrolatum ointment were divided randomly into three groups: Group A: 33 patients treated for single day (24 hours); Group B: 32 patients treated for three successive nights (from 6 p.m. to 8 p.m. to 6 a.m. to 8 a.m. and bathing every day); and Group C: 32 patients treated for three successive days (bathing every 24 hours). The patients were seen regularly every two weeks for the duration of four weeks. RESULTS: Study included 58 (59.8%) males and 39 (40.2%) females, with a male to female ratio 1.4:1. The age range of males at presentation from 3 to 64 (26.74±15.98) years, while the females age ranged at presentation from 3 to 60 (24.05±14.53) years of age. At the end of the study, the response to treatment was: Group A, response in 14 (42.4%) patients and no response in 19 (57.6%); Group B, response in 29 (90.6%) patients and no response in 3 (9.4%); and Group C, response in 31 (96.9%) patients and no response in 1 (3.1%). There is significant statistical difference among the response of 3 groups with (P=0.00000011), but no statistically significant difference between the response of Group C and Group B, (P=0.6055). Mild burning sensation and irritating (sulfur) dermatitis were the only side effects of 8% and 10% sulfur. Pruritic rash occurred in Group C mainly, in 11 (34.4%) patients, 8 (25%) in Group B and 4 (12.1%) in Group A, with no significance (P=0.1058). Recurrence or relapse occurred in Group A mainly, with 4 (12.1%) patients, and in Group B, 1 patient, (3.1%), with no recurrence in group C, with significance (P=0.0060). CONCLUSION: Three successive days and three successive nights of 8% and 10% sulfur ointment were effective regimens with no statistical difference in favor of three successive days, while single-day application was much less effective but with fewer side effects.

Health-Related Quality of Life (HRQoL) of Residents with Persistent Lower Respiratory Symptoms or Asthma Following a Sulphur Stockpile Fire Incident.

Background: This study evaluated health-related quality of life (HRQoL) in residents with persistent lower respiratory symptoms (PLRS) or asthma six years after exposure to sulphur dioxide vapours emanating from an ignited sulphur stockpile. Methods: A cross-sectional study was carried out, using interview data collected at three time points (prior to, one- and six-years post incident), medical history, respiratory symptoms and HRQOL using the Medical Outcomes Study Form 36 (SF-36). Results: A total of 246 records, 74 with and 172 without PLRS or asthma, were analysed. The mean age was 42 (SD:12) years in the symptomatic group and 41 (SD:13) years in the asymptomatic group. Mean SF-36 scores were significantly lower for the symptomatic group in the Physical Functioning (24 vs. 39), Role-Physical (33 vs. 48) and General Health (GH) domains (24 vs. 37). Symptomatic residents experienced a significant decline in their Role-Physical (OR = 1.97; CI 1.09, 3.55) and GH (OR = 3.50; CI 1.39, 8.79) at year 6 compared to asymptomatic participants. Residents with co-morbid reactive upper airways dysfunction syndrome demonstrated stronger associations for GH (OR = 7.04; CI 1.61, 30.7) at year 1 and at year 6 (OR = 8.58; CI 1.10, 65.02). Conclusions: This study highlights the long-term adverse impact on HRQoL among residents with PLRS or asthma following a sulphur stockpile fire disaster.

Potential of sulfur-selenium isosteric replacement as a strategy for the development of new anti-chagasic drugs.

Current treatment for Chagas disease is based on only two drugs: benznidazole and nifurtimox. Compounds containing sulfur (S) in their structure have shown promising results in vitro and in vivo against Trypanosoma cruzi, the parasite causing Chagas disease. Notably, some reports show that the isosteric replacement of S by selenium (Se) could be an interesting strategy for the development of new compounds for the treatment of Chagas disease. To date, the activity against T. cruzi of three Se- containing groups has been compared with their S counterparts: selenosemicarbazones, selenoquinones, and selenocyanates. More studies are needed to confirm the positive results of Se compounds. Therefore, we have investigated S compounds described in the literature tested against T. cruzi. We focused on those tested in vivo that allowed isosteric replacement to propose their Se counterparts as promising compounds for the future development of new drugs against Chagas disease.

Refractory Helicobacter pylori infection and the gastric microbiota.

Background: Curing refractory Helicobacter pylori infection is difficult. In addition, there is currently no research on the gastric microbiota of refractory H. pylori infection. Methods: We designed a clinical retrospective study involving 32 subjects divided into three groups: 1. nAGHp.a, treatment-naïve patients with H. pylori infection; 2. nAGHp.b, H. pylori-negative patients; and 3. EFHp.a, patients with refractory H. pylori infection. Gastric mucosal samples from the biobank of our research center were collected for 16S rRNA sequencing analysis and bacterial functions were predicted via PICRUSt. Results: There were significant differences between the H. pylori- positive group and the H. pylori-negative group in species diversity, gastric microbiota structure, and bacterial function. The beneficial Lactobacillus in the H. pylori-positive group were significantly enriched compared with those in the refractory H. pylori infection group. The bacterial interaction network diagram suggested that the microbiota interactions in the refractory H. pylori infection group decreased. The gastric microbiota of the refractory H. pylori infection group was enriched in the pathways of metabolism and infectious diseases (energy metabolism, bacterial secretion system, glutathione metabolism, protein folding and associated processing, sulphur metabolism, membrane and intracellular structural molecules, lipopolysaccharide biosynthesis, ubiquinone and other terpenoid-quinone biosynthesis, inorganic ion transport and metabolism, and metabolism of cofactors and vitamins) when compared with the H. pylori-positive group without treatment based on PICRUSt analysis. Conclusion: Significant alterations occurred in the gastric microbiota when eradication of H. pylori failed multiple times. A history of eradication of multiple H. pylori infections leads to an imbalance in the gastric mucosal microbiota to a certain extent, which was mainly reflected in the inhibition of the growth of beneficial Lactobacillus in the stomach. Patients with refractory H. pylori infection may be at a higher risk of developing gastric cancer than other H. pylori-positive patients.

Study of the anticancer potential of Cd complexes of selenazoyl-hydrazones and their sulfur isosters.

The biological activity of Cd compounds has been investigated scarce since Cd has been recognized as a human carcinogen. However, the toxicity of cadmium is comparable to the toxicity of noble metals such as Pt and Pd. The paradigm of metal toxicity has been challenged suggesting that metal toxicity is not a constant property, yet it depends on many factors like the presence of appropriate ligands. Studies on anticancer activity of cadmium complexes showed that the complexation of various ligands resulted in complexes that showed better activities than approved drugs. In the present study, cadmium complexes with biologically potent thiazolyl/selenazoyl-hydrazone ligands have been prepared, and tested for their activity against different types of tumor cell models. The complexation of ligands with Cd(II) resulted in a synergistic effect. The antiproliferative activity study revealed that all complexes are more active compared to 5-fluorouracil and cisplatin. The mechanism of tumor cell growth inhibition reveal that selenium-based compounds induce cell death in T-47D (gland carcinoma) cells through apoptosis via caspase-3/7 activation. Additionally, their pro-apoptotic effect was stronger compared to etoposide and cisplatin. Nuclease activity, detected by gel electrophoresis, may be the possible mechanism of anticancer action of investigated complexes.

Coordinated Transcriptional and Catabolic Programs Support Iron-Dependent Adaptation to RAS-MAPK Pathway Inhibition in Pancreatic Cancer.

The mechanisms underlying metabolic adaptation of pancreatic ductal adenocarcinoma (PDA) cells to pharmacologic inhibition of RAS-MAPK signaling are largely unknown. Using transcriptome and chromatin immunoprecipitation profiling of PDA cells treated with the MEK inhibitor (MEKi) trametinib, we identify transcriptional antagonism between c-MYC and the master transcription factors for lysosome gene expression, the MiT/TFE proteins. Under baseline conditions, c-MYC and MiT/TFE factors compete for binding to lysosome gene promoters to fine-tune gene expression. Treatment of PDA cells or patient organoids with MEKi leads to c-MYC downregulation and increased MiT/TFE-dependent lysosome biogenesis. Quantitative proteomics of immunopurified lysosomes uncovered reliance on ferritinophagy, the selective degradation of the iron storage complex ferritin, in MEKi-treated cells. Ferritinophagy promotes mitochondrial iron-sulfur cluster protein synthesis and enhanced mitochondrial respiration. Accordingly, suppressing iron utilization sensitizes PDA cells to MEKi, highlighting a critical and targetable reliance on lysosome-dependent iron supply during adaptation to KRAS-MAPK inhibition. SIGNIFICANCE: Reduced c-MYC levels following MAPK pathway suppression facilitate the upregulation of autophagy and lysosome biogenesis. Increased autophagy-lysosome activity is required for increased ferritinophagy-mediated iron supply, which supports mitochondrial respiration under therapy stress. Disruption of ferritinophagy synergizes with KRAS-MAPK inhibition and blocks PDA growth, thus highlighting a key targetable metabolic dependency. See related commentary by Jain and Amaravadi, p. 2023. See related article by Santana-Codina et al., p. 2180. This article is highlighted in the In This Issue feature, p. 2007.

Efficiency of sulphur in garlic extract and non-sulphur homeopathy in the control of the cattle tick Rhipicephalus (Boophilus) microplus.

The objective of the present work was to evaluate the efficacy of a non-sulphur-based homeopathic preparation and a sulphur-containing natural product derived from Allium sativum (Linnaeus) against infestation by the cattle tick Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae). A total of 24 crossbred calves (7 : 8 Holstein : Zebu), aged 6-8 months and maintained in individual stables under tick-free conditions, were divided into three groups. Group 1 (control group) received no treatment; Group 2 was treated with 0.01 g/day of the homeopathic preparation Fator C&MC(®), and Group 3 was treated with 20 g/day of Enxofre-Allium sativum(®). After adaptation to the diet for 1 month, each calf was subjected to artificial infestation with 8000 R. (B.) microplus larvae (aged 7-14 days) twice per week over a 5-month period. Numbers of engorged females were recorded every 14 days and samples of freely released engorged females were collected at 14-day intervals commencing 3 months after the start of the experiment. The engorged females were weighed, incubated for 15 days under biochemical oxygen demand conditions at 27 ± 1 °C and relative humidity >85%, and the weights of the egg masses produced were recorded. Other biological parameters, including reproduction estimate, reduction in oviposition and efficiency of treatment, were determined. A significant reduction in the number of engorged females was detected on animals treated with Enxofre-Allium sativum(®) (Group 3) in comparison with the other two groups. The overall efficiency of the treatment with the sulphur-containing product was 64%, whereas that of the homeopathic preparation was 26%. Under the experimental conditions established, Enxofre-Allium sativum(®) can reduce the intensity of the R. (B.) microplus infestation.