Geriatric cutaneous leishmaniasis: a retrospective analysis of 622 cases.

BACKGROUND: Cutaneous leishmaniasis (CL) is most common in childhood because children are exposed to the parasite early and, unlike adults, do not have immunity to CL. Since CL is less common in geriatric patients, clinical and epidemiological data in this age group are limited. This study aims to compare the clinical and demographic characteristics of geriatric patients diagnosed with CL with young patients. METHODS: In this retrospective study, 622 patients aged 65 and over and 6350 patients aged 19-64, who applied to Sanliurfa Oriental Boil Diagnosis and Treatment Center between January 2013 and February 2024 and were diagnosed with CL by parasitological examination, were included. Clinical and demographic characteristics of patients diagnosed with CL, such as age, gender, location of the lesion, lesion size, duration of the lesion, and treatments applied due to the diagnosis of CL, were recorded. Clinical and demographic characteristics of geriatric and young patients were compared. RESULTS: The mean age of elderly CL cases was 72.95 ± 6.54 years, and 65.2% were female. The most common clinical forms were ulcers (51.9%) and plaques (41%), respectively, in young and elderly patients. The most common locations of the lesions were upper limbs (54.8%) in all patients. The most preferred treatment method was intralesional (IL) meglumine antimoniate (MA) treatment (98.3%) in all patients. There were no difference between young and elderly CL cases in terms of mean number of lesions, average lesion duration, average lesion size, lesion location, clinical forms of lesions, and treatments options (P > 0.05). CONCLUSIONS: Based on the results of our study, it can be said that the clinical and demographic characteristics of CL are similar in young and old patients and systemic MA treatment shows similar clinical benefit in both age groups. In addition, it can be said that systemic MA therapy can be used safely in young patients and elderly patients without contraindications. IL MA therapy can be used in elderly patients where systemic MA therapy is contraindicated.

Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

Treatment of mucocutaneous leishmaniasis - A systematic review.

Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities. It is caused by protozoa of the genus Leishmania spp. transmitted to humans by sandflies. Mucocutaneous leishmaniasis occurs after untreated or inadequately treated cutaneous leishmaniasis and is more common in immunocompromised patients. The aim of this systematic review is to summarize all reported treatment options for mucocutaneous leishmaniasis. This review is based on all English, German, French, Spanish and Portuguese articles published in the databases "PubMed" and "Lilacs" from 1995 to 2020. Most of the medical literature is limited to case reports, small case series, retrospective studies, and a few randomized controlled trials. Various treatment options include pentavalent antimonates such as meglumine antimonate or sodium stibogluconate, amphotericin B (liposomal, deoxycholate, lipid complex, colloidal dispersion), miltefosine, and pentamidine. Other therapeutic options include itraconazole, fluconazole, ketoconazole, aminosidine sulfate, and azithromycin. The choice of drug depends primarily on its availability in the endemic area and the patient's comorbidities.

[Use of meglumine sodium succinate and NPWT therapy in the treatment of early and late complications of cholelistics]. / Ispol'zovanie meglyumina natriya suktsinata i NRWT-terapii v lechenii rannikh i pozdnikh oslozhnenii zhelchnokamennoi bolezni.

Gallstone disease remains an important medical and socially significant problem due to the increase in the proportion of patients of young and working age. At the same time, along with the increase in incidence, the number of complicated forms, such as choledocholithiasis in combination with stenosing duodenal papillitis (SDP) and obstructive jaundice, is increasing, which increases the importance of surgical approaches in the complex treatment of the disease and expands the range of conservative methods of therapy. In the given clinical observation of a young patient with severe cholelithiasis, accompanied by early and late complications, including the formation of postoperative scars and ventral hernias. At the last of the described stages of treatment during allohernioplasty, a complication developed in the form of a seroma followed by phlegmon of the anterior abdominal wall in the area of the implant, which served as the basis for including both local (NPWT therapy) and general (a course of infusions of a succinate-containing drug) methods in the treatment regimen, which contributed to more pronounced positive dynamics of the patient's condition.

A Randomized, Controlled, Noninferiority, Multicenter Trial of Systemic vs Intralesional Treatment With Meglumine Antimoniate for Cutaneous Leishmaniasis in Brazil.

BACKGROUND: Meglumine antimoniate (MA) remains the main treatment for cutaneous leishmaniasis (CL). Uncontrolled studies suggest that intralesional MA (IL-MA) may be noninferior and safer than systemic MA (S-MA). METHODS: Multicenter, randomized, controlled, open-label, phase 3 clinical trial to evaluate the efficacy and toxicity of IL-MA in 3 infiltrations at 14-day intervals compared with S-MA (10-20 mg Sb5+/kg/day, 20 days) for CL, with noninferiority margin of 20%. Primary and secondary outcomes were definitive cure at day 180 and epithelialization rate at day 90 of treatment, respectively. A 2-year follow-up was performed to assess relapses and emergence of mucosal lesions. Adverse events (AEs) were monitored according to the Division of AIDS AE grading system. RESULTS: We evaluated 135 patients. The cure rates (95% confidence interval) for IL-MA and S-MA treatment were, respectively, 82.8% (70.5-91.4) and 67.8% (53.3-78.3) per protocol (PP) and 70.6% (58.3-81.0) and 59.7% (47.0-71.5) per intention to treat (ITT). The epithelialization rates of the IL-MA and S-MA treatment were, respectively, 79.3% (66.6-88 + 8) and 71.2% (57.9-82.2) PP and 69.1% (55.2-78.5) and 64.2% (50.0-74.2) ITT. AEs in the IL-MA and S-MA groups were, respectively, clinical, 45.6% and 80.6%; laboratory, 26.5% and 73.1%; and electrocardiogram, 8.8% and 25.4%. Ten participants in the S-MA group and 1 in the IL-MA group were discontinued due to severe or persistent AEs. CONCLUSIONS: IL-MA provides a similar cure rate and results in less toxicity compared with S-MA and may be used as first-line therapy for CL patients. CLINICAL TRIALS REGISTRATION: REBEC: RBR-6mk5n4.

An analysis of silybin meglumine tablets in the treatment of drug-induced liver injury as assessed for causality with the updated Roussel Uclaf Causality Assessment Method using a nationwide database.

AIM: Drug-induced liver injury (DILI) poses significant challenges to clinical practice. Currently, there is no recommended therapy to treat DILI; therefore, it is vital to explore new therapeutic agents. This study aimed to investigate the efficacy and safety of silybin meglumine tablets in treating DILI. METHODS: This study analysed 34 296 DILI cases assessed by the updated RUCAM from a nationwide database. A total of 301 patients with RUCAM scores ≥6 were directly enrolled in this study, while an additional 340 patients with RUCAM scores <6 who were adjudged as probable DILI by a panel of three hepatologists were also included in the analysis. The enrolled patients were divided into the silybin meglumine group and the control group. The propensity score matching (PSM) method was used to obtain comparable characteristics between the two groups. RESULTS: There were 129 cases in the silybin meglumine group and 512 cases in the control group. After applying PSM, 129 matched pairs were obtained. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) resumption rates in the silybin meglumine group were significantly higher than the control group (58.91% vs. 20.93%, P ≤ .0001 and 63.49% vs. 37.50%, P ≤ .0001). The univariate and multivariate logistic regression analysis revealed that grouping factor (odds raio [OR], 5.42; 95% confidenxe interval [CI], 3.12-9.39; P < .0001 and OR, 6.10; 95% CI, 2.98-12.48; P < .0001) and ALT levels (OR, 0.95; 95% CI, 0.93-0.98; P = .0015 and OR, 0.95; 95% CI, 0.92-0.99; P = .0157) were essential influencing factors for ALT normalization. CONCLUSIONS: Silybin meglumine tablets are safe and effective in DILI treatment. Large-scale and randomized controlled trials are required to further confirm their efficacy.

Pre-clinical Formulation Development of an in situ Meglumine Salt of AZD5991: A Novel Macrocyclic Mcl-1 Inhibitor.

PURPOSE: AZD5991 is a potent and selective macrocyclic inhibitor of Mcl-1 in clinical development. Developing an intravenous solution formulation for AZD5991 proved to be challenging primarily due to the poor intrinsic solubility of AZD5991. In this article are described studies performed to select a suitable crystalline form and to assess physicochemical properties of AZD5991 to aid in the design of a solution formulation for preclinical studies. METHODS: It is preferable that the preclinical formulation has a line of sight for clinical formulation. For AZD5991, a concentration of at least 20 mg/ml was required for toxicology studies. Toward this goal, extensive pre-formulation characterization of AZD5991 including solid form analysis, pH-solubility profiling and solubility determination in cosolvents and other solubilizing media were carried out. RESULTS & DISCUSSION: Crystalline Form A, which is more stable in aqueous solution and possesses acceptable thermal stability, was selected for preclinical and clinical development of AZD5991. Extensive solubility evaluation revealed an interesting pH-solubility profile that significantly enhances solubilization at pH > 8.5 to allow solution concentrations of at least 30 mg/ml by in situ meglumine salt formation. CONCLUSION: Developing pre-clinical formulations to support in vivo studies requires a good understanding of the physicochemical properties of the drug candidates. Candidates with challenging pharmaceutic properties like the novel macrocycle molecule AZD5991, demand extensive characterization in its polymorph landscape, solubility profile and suitability evaluation of the excipients. Meglumine, a pH-adjusting and solubilizing agent, was found to be the best choice for formulating AZD5991 into an intravenous product to support preclinical studies.

Transcrocetin Meglumine Salt Inhibits Spinal Glial Cell-Mediated Proinflammatory Cytokines and Attenuates Complete Freund's Adjuvant-Induced Inflammatory Pain.

INTRODUCTION: Inflammatory pain is a significant global clinical challenge that involves both unpleasant sensory and emotional experiences. The treatment of pain is imminent, and we are committed to seeking new analgesics for pain relief. Transcrocetin meglumine salt (TCMS), a saffron metabolite derived from the crocin apocarotenoids, has exhibited the ability to cross the blood-brain barrier and exert neuroprotective effects. In this study, we aimed to investigate whether TCMS could ameliorate complete Freund's adjuvant (CFA)-induced inflammatory pain in mice and elucidate its underlying mechanisms. METHODS: Here, we established an inflammatory pain model in mice by injecting CFA into the left hind paw. Three days later, we administered intraperitoneal injections of TCMS (10 mg/kg) or saline to the animals. We examined mechanical allodynia, thermal hypersensitivity, and anxiety behavior. Furthermore, the activation of glial cells and proinflammatory cytokines in the spinal cord were detected. RESULTS: Our results showed that TCMS significantly reversed the mechanical allodynia and thermal hypersensitivity in the CFA-injected mice. Furthermore, TCMS administration effectively inhibited the activation of microglia and astrocytes in the spinal cord induced by CFA. Additionally, TCMS suppressed the production and release of spinal proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6, in CFA-injected mice. CONCLUSION: Taken together, our findings demonstrate that TCMS holds promise as an innovative analgesic due to its ability to ameliorate inflammatory reactions.

The potential of intravenous topiramate for the treatment of status epilepticus.

There is considerable clinical evidence that topiramate (TPM) has a high potential in the treatment of refractory and super-refractory status epilepticus (RSE, SRSE). Because TPM is only approved for oral administration, it is applied as suspension via a nasogastric tube for SE treatment. However, this route of administration is impractical in an emergency setting and leads to variable absorption with unpredictable plasma levels and time to peak concentration. Thus, the development of an intravenous (i.v.) solution for TPM is highly desirable. Here we present data on two parenteral formulations of TPM that are currently being developed. One of these solutions is using sulfobutylether-ß-cyclodextrin (SBE-ß-CD; Captisol®) as an excipient. A 1% solution of TPM in 10% Captisol® has been reported to be well tolerated in safety studies in healthy volunteers and patients with epilepsy or migraine, but efficacy data are not available. The other solution uses the FDA- and EMA-approved excipient amino sugar meglumine. Meglumine is much more effective to dissolve TPM in water than Captisol®. A 1% solution of TPM can be achieved with 0.5-1% of meglumine. While the use of Captisol®-containing solutions is restricted in children and patients with renal impairment, such restrictions do not apply to meglumine. Recently, first-in-human data were reported for a meglumine-based solution of TPM, indicating safety and efficacy when used as a replacement for oral administration in a woman with epilepsy. Based on the multiple mechanisms of action of TPM that directly target the molecular neuronal alterations that are thought to underlie the loss of efficacy of benzodiazepines and other anti-seizure medications during prolonged SE and its rapid brain penetration after i.v. administration, we suggest that parenteral (i.v.) TPM is ideally suited for the treatment of RSE and SRSE. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Effects of a single transdermal administration of flunixin meglumine in early postpartum Holstein Friesian dairy cows: Part 1. Inflammatory and metabolic markers, uterine health, and indicators of pain.

The objectives of this study were to assess the effects of a single transdermal administration of flunixin meglumine (FM) in early postpartum Holstein Friesian dairy cows on serum concentrations of inflammatory and metabolic markers, uterine health, and indicators of pain. The hypothesis was that the anti-inflammatory, antipyretic, and analgetic effects of the pharmaceutic agent would reduce systemic inflammation, resulting in improved metabolic and inflammatory profile, diminished incidence of metritis, and reduced expression of pain. A total of 500 cows (153 primiparous, 347 multiparous) from 3 different commercial dairy farms in the northeast of Germany were included in a randomized controlled clinical trial. Farms were preselected based on high haptoglobin concentrations in their fresh lactating cows. Cows were excluded if they had experienced dystocia, stillbirth, or twin birth, or if they showed any signs of milk fever, retained fetal membranes, or fever (>40°C). The cows were treated once with either FM (3.33 mg/kg) or a placebo as control (CON) through transdermal administration between 24 to 36 h postpartum (d 2). General health examinations were performed (daily from d 2-8 and additionally on d 15 postpartum), vaginal discharge was assessed using the Metricheck device (d 8 and 15 postpartum) and serum samples were analyzed for inflammatory and metabolic markers (d 2, 4, and 6 postpartum). Effects of treatment, parity, sampling day, and their interactions were evaluated using mixed effects models. Primiparous cows treated with FM showed lower serum haptoglobin concentrations (0.90 ± 0.08 vs. 1.17 ± 0.07 g/L; ± standard error of the mean) and higher serum albumin concentrations (35.5 ± 0.31 vs. 34.8 ± 0.31 g/L) on d 6 postpartum. They also had a lower risk for purulent vaginal discharge with or without a fever compared with CON cows on d 15 postpartum (odds ratio for CON vs. FM: 1.63, 95% CI: 1.26-2.00), and body temperature was lower throughout the first 15 d in milk (39.1 ± 0.11 vs. 39.2 ± 0.11°C). Multiparous cows treated with FM had lower serum ß-hydroxybutyrate concentrations on d 4 postpartum (0.71 ± 0.05 vs. 0.78 ± 0.05 mmol/L) and d 6 postpartum (0.74 ± 0.05 vs. 0.80 ± 0.05 mmol/L). Regardless of parity, FM-treated cows were significantly less likely to abduct their tail from their body (14.3 vs. 23.6%) and show an arched back (27.9 vs. 39.7%) on the day after treatment compared with CON cows. It can be concluded that FM treatment slightly reduced inflammation and diminished the risk for metritis in primiparous cows, improved metabolic profile in multiparous cows, and reduced expressions of pain in all cows.

Lipolysis inhibition as a treatment of clinical ketosis in dairy cows: A randomized clinical trial.

Excessive and protracted lipolysis in adipose tissues of dairy cows is a major risk factor for clinical ketosis (CK). This metabolic disease is common in postpartum cows when lipolysis provides fatty acids as an energy substrate to offset negative energy balance. Lipolysis in cows can be induced by the canonical (hormonally induced) and inflammatory pathways. Current treatments for CK focus on improving glucose in blood (i.e., oral propylene glycol [PG], or i.v. dextrose). However, these therapies do not inhibit the canonical and inflammatory lipolytic pathways. Niacin (NIA) can reduce activation of the canonical pathway. Blocking inflammatory responses with cyclooxygenase inhibitors such as flunixin meglumine (FM) can inhibit inflammatory lipolytic activity. The objective of this study was to determine the effects of including NIA and FM in the standard PG treatment for postpartum CK on circulating concentrations of ketone bodies. A 4-group, parallel, individually randomized trial was conducted in multiparous Jersey cows (n = 80) from a commercial dairy in Michigan during a 7-mo period. Eligible cows had CK symptoms (lethargy, depressed appetite, and milk yield) and hyperketonemia (blood ß-hydroxybutyrate [BHB] ≥1.2 mmol/L). Cows with CK were randomly assigned to 1 of 3 groups where the first group received 310 g of oral PG once per day for 5 d; the second group received PG for 5 d + 24 g of oral NIA once per day for 3 d (PGNIA); and the third group received PG for 5 d + NIA for 3 d + 1.1 mg/kg i.v. FM once per day for 3 d (PGNIAFM). The control group consisted of cows that were clinically healthy (HC; untreated; BHB <1.2 mmol/L, n = 27) matching for parity and DIM with all 3 groups. Animals were sampled at enrollment (d 0), and d 3, 7, and 14 to evaluate ketone bodies and circulating metabolic and inflammatory biomarkers. Effects of treatment, sampling day, and their interactions were evaluated using mixed effects models. Logistic regression was used to calculate the odds ratio (OR) of returning to normoketonemia (BHB <1.2 mmol/L). Compared with HC, enrolled CK cows exhibited higher blood concentrations of dyslipidemia markers, including nonesterified fatty acids (NEFA) and BHB, and lower glucose and insulin levels. Cows with CK also had increased levels of biomarkers of pain (substance P), inflammation, including lipopolysaccharide-binding protein, haptoglobin, and serum amyloid A, and proinflammatory cytokines IL-4, MCP-1, MIP-1α, and TNFα. Importantly, 72.2% of CK cows presented endotoxemia and had higher circulating bacterial DNA compared with HC. By d 7, the percentage of cows with normoketonemia were higher in PGNIAFM = 87.5%, compared with PG = 58.33%, and PGNIA = 62.5%. At d 7 the OR for normoketonemia in PGNIAFM cows were 1.5 (95% CI, 1.03-2.17) and 1.4 (95% CI, 0.99-1.97) relative to PG and PGNIA, respectively. At d 3, 7, and 14, PGNIAFM cows presented the lowest values of BHB (PG = 1.36; PGNIA = 1.24; PGNIAFM = 0.89 ± 0.13 mmol/L), NEFA (PG = 0.58; PGNIA = 0.59; PGNIAFM = 0.45 ± 0.02 mmol/L), and acute phase proteins. Cows in PGNIAFM also presented the highest blood glucose increment across time points and insulin by d 7. These data provide evidence that bacteremia or endotoxemia, systemic inflammation, and pain may play a crucial role in CK pathogenesis. Additionally, targeting lipolysis and inflammation with NIA and FM during CK effectively reduces dyslipidemia biomarkers, improves glycemia, and improves overall clinical recovery.

Effects of a single transdermal administration of flunixin meglumine in early postpartum Holstein Friesian dairy cows: Part 2. Milk yield, culling risk, and reproductive performance.

This study was conducted to assess the effects of a single transdermal administration of flunixin meglumine (FM) in early postpartum Holstein Friesian dairy cows on milk yield, culling risk, and reproductive performance. We hypothesized that FM treatment would reduce systemic inflammation, leading to higher milk yield, reduced culling risk, and better reproductive performance in the subsequent lactation. Holstein Friesian dairy cows [n = 500, 153 primiparous (PRIM), 347 multiparous (MULT)] from 3 farms in northeast Germany were enrolled in a prospective, randomized controlled clinical trial. Farms at risk for cows with excessive postpartum inflammation were identified in a preliminary trial by measuring serum haptoglobin concentrations in their fresh lactating cows. Only cows that had a eutocic birth and delivered a singleton calf alive, with no signs of milk fever or retained fetal membranes and rectal temperature ≤40°C at first clinical examination, were included within 24 to 36 h postpartum. Treatment included a single transdermal administration of either FM (3.33 mg/kg) or a placebo as control (CON). Milk production, milk solids, urea, and somatic cell count were recorded monthly for 8 mo after calving. Culling risk, first-service conception risk, and days open were retrieved from the farms' herd management software. Separate models for PRIM and MULT cows were built for most parameters because of significant effects of parity and parity × treatment interaction. Energy-corrected milk yield from 8 monthly Dairy Herd Improvement-equivalent tests was slightly greater in PRIM cows treated with FM (29.51 and 30.73 ± 1.35 kg, CON vs. FM), whereas it was reduced in treated MULT cows (38.23 and 37.47 ± 1.17 kg, CON vs. FM) compared with CON. Milk fat and protein yields were greater in FM-treated PRIM cows and lower in treated MULT cows compared with CON. Milk urea and somatic cell count were not affected by treatment. No differences in culling risk, first-service conception risk, or days open were observed. We conclude that a single transdermal administration of FM in early postpartum dairy cows on farms at risk for excessive postpartum inflammation slightly increased milk, milk fat, and milk protein yields in PRIM cows and decreased these variables in MULT cows. Neither culling risk nor fertility was affected by treatment in this study.

Treatment with 2 commercial antibiotics reduced clinical and systemic signs of pneumonia and the abundance of pathogenic bacteria in the upper respiratory tract of preweaning dairy calves.

The aim of this study was to evaluate the effect of therapeutically administered tildipirosin or florfenicol + flunixin meglumine for the treatment of bovine respiratory disease (BRD) accompanied by fever in calves before weaning compared with diseased and untreated animals. As specific objectives, we evaluated the composition of the bacterial microbiota of the upper respiratory tract (URT) and blood and health parameters of the animals. Preweaning Holstein female calves diagnosed with naturally acquired pneumonia were randomly assigned to one of the following experimental groups on the day of diagnosis (d 0): (1) TLD (n = 36): single subcutaneous injection with 4 mg/kg tildipirosin; (2) FLF (n = 33): single subcutaneous injection with an antimicrobial (40 mg/kg florfenicol) combined with a nonsteroidal anti-inflammatory drug (2.2 mg/kg flunixin meglumine); and (3) NEG (n = 35): no treatment within the first 5 d following enrollment. The NEG treatment group was closely monitored for 5 d, and calves were removed from the study following a standardized late treatment protocol, when necessary, to minimize health concerns. Healthy untreated calves (CTR; n = 31) were also selected for the study and used as controls. Blood samples used for biochemical analysis and nasopharyngeal swabs used for evaluation of URT microbiota were collected daily from d 0 until d 5 and then weekly until weaning. Next-generation sequencing of the 16S rRNA gene was used to assess the URT microbiota at the phylum and genus levels. Clinical signs associated with pneumonia and otitis media were assessed daily, as was the need for antibiotic interventions. Calves in the TLD and FLF groups had faster recovery from fever within the first 5 d after enrollment. In addition, antibiotic-treated calves reached the same serum haptoglobin levels as healthy calves on d 2 after diagnosis, whereas calves in the NEG group had higher haptoglobin levels than the CTR group until at least d 5 after BRD diagnosis. Calves in the TLD and FLF groups had a lower risk of treatment for pneumonia (FLF = 22.8%; TLD = 27.7%) from d 5 to weaning than calves in the NEG group (54.7%). Furthermore, FLF treatment had a significantly lower risk of nasal discharge, otitis media, and treatment failure compared with the NEG group, but did not differ from the TLD group. Differences in the composition of the URT microbiota were found between groups, and the genus Mycoplasma was the most abundant in samples collected from the URT of calves with and without pneumonia. Both drugs were effective in reducing the mean relative abundance (MRA) of important genera associated with pneumonia (Mannheimia and Pasteurella), although an increase in Mycoplasma MRA was observed for tildipirosin-treated calves. In conclusion, both drugs were effective in reducing the inflammatory signs of pneumonia and the need for antimicrobial treatment after enrollment compared with no treatment. In addition, both TLD and FLF were effective in reducing the MRA of important bacterial genera associated with pneumonia; however, TLD treatment was associated with increased Mycoplasma MRA compared with healthy and untreated calves.

Antiplatelet effect of ginkgo diterpene lactone meglumine injection in acute ischemic stroke: A randomized, double-blind, placebo-controlled clinical trial.

This study was designed to evaluate antiplatelet effect and therapeutic effect of ginkgo diterpene lactone meglumine injection (GDLI) in acute ischemic stroke (AIS) patients. In this randomized, double-blind, placebo-controlled trial, we randomly assigned 70 inpatients within 48 hr after the onset of AIS to combination therapy with GDLI and aspirin (GDLI at a dose of 25 mg/d for 14 days plus aspirin at a dose of 100 mg/d for 90 days) or to placebo plus aspirin in a ratio of 1:1. Platelet function, the National Institute of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were evaluated. A good outcome was defined as NIHSS scores decrease ≥5 or mRS scores decrease ≥2. Results showed that arachidonic acid induced maximum platelet aggregation rate (AA-MAR) and mean platelet volume (MPV) of the GDLI-aspirin group were much lower than that of the aspirin group (p = 0.013 and p = 0.034, respectively) after the 14-day therapy. The combination of GDLI and aspirin was superior to aspirin alone, and had significant impact on the good outcome at day 90 (ORadj 7.21 [95%CI, 1.03-50.68], p = 0.047). In summary, GDLI has antiplatelet effect and can improve the prognosis of AIS patients.

Neuroprotective effect of meglumine cyclic adenylate against ischemia/reperfusion injury via STAT3-Ser727 phosphorylation.

OBJECTIVES: Ischemia/reperfusion can induce neuronal apoptosis in the brain and lead to function deficits. The activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is neuroprotective against transient cerebral ischemia. The neuroprotective mechanisms of PKA mainly involve the regulation of gene transcription via the PKA/CREB pathway. The present study aims to investigate the neuroprotective effect of meglumine cyclic adenylate, an activator of PKA, under a rat model of global cerebral ischemia/reperfusion and to reveal the underlying mechanism involving signal transducer and activator of transcription 3 (STAT3)-Ser727 phosphorylation and mitochondrion modulation. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to 15 min global cerebral ischemia, and meglumine cyclic adenylate was treated through tail intravenous injection 30 min before ischemia. Cresyl violet staining was used to evaluate neuron injury at 5 d of reperfusion. Western blotting was used to detect p-Ser727-STAT3, total STAT3, cytochrome c (Cyt c) and active caspase-3 in the tissues of hippocampal CA1 region at 6 h of reperfusion. STAT3-S727A was overexpressed in HT22 cells to reveal the significance of STAT3-Ser727 phosphorylation in the neuroprotective effect of meglumine cyclic adenylate. RESULTS: Pretreatment with meglumine cyclic adenylate not only significantly ameliorated neuron loss in CA1 region after global cerebral ischemia but also enhanced STAT3-Ser727 phosphorylation, increased mitochondrial STAT3, and decreased cytosolic Cyt c and active caspase-3. Overexpression of STAT3-S727A in HT22 cells eliminated meglumine cyclic adenylate-induced increase of p-Ser727-STAT3, mitochondrial STAT3, cytosolic Cyt c and active caspase-3. CONCLUSION: Meglumine cyclic adenylate protects neurons against ischemia/reperfusion injury via promoting p-Ser727-STAT3-associated mitochondrion modulation and inhibiting apoptosis pathway.

Development and evaluation of febuxostat solid dispersion through screening method.

Febuxostat (Febux) is a BCS II drug and has a very low solubility. In order to overcome this shortcoming, the purpose of study is to increase the in vitro dissolution (%) and drug release (%) of Febux by using a screening method. The Febux-SD formulation was prepared by screening solubilizers, pH agents, and carriers using with a solvent evaporation method. The novel Febux SD formulation was successfully developed. The dissolution (%) of Febux of optimal formulation (SD3) was higher than that of Feburic® tab in pH 1.2, distilled water (DW), and pH 6.8 buffer by 6.3-, 2.6-, and 1.1-fold, respectively, at 60 min. The in vitro drug release (%) and permeability (µg/cm2) of SD3 formulation were improved compared to those of Feburic® tab in the pH shifting method and PBS (7.4), respectively. The SD3 formulation was well maintained the stability for 6 months, and that of physicochemical properties were altered. In conclusion, the Febux solubilization study with meglumine was first attempted and successfully performed. Through the improved dissolution (%) of Febux, high bioavailability of SD3 formulation is expected in animal and human studies.

Enforced Electronic-Donor-Acceptor Complex Formation in Water for Photochemical Cross-Coupling.

The amino alcohol meglumine solubilizes organic compounds in water and enforces the formation of electron donor acceptor (EDA) complexes of haloarenes with indoles, anilines, anisoles or thiols, which are not observed in organic solvents. UV-A photoinduced electron transfer within the EDA complexes induces the mesolytic cleavage of the halide ion and radical recombination of the arenes leading, after rearomatization and proton loss to C-C or C-S coupling products. Depending on the substitution pattern selective and unique cross-couplings are observed. UV and NMR measurements reveal the importance of the assembly for the photoinduced reaction. Enforced EDA aggregate formation in water allows new activation modes for organic photochemical synthesis.

[The effectiveness of vacuum therapy and meglumine sodium succinate in unformed fistulas of the gastrointestinal tract (clinical observations)]. / Effektivnost' primeneniya vakuum-terapii i meglyumina natriya suktsinata pri nesformirovannykh svishchakh zheludochno-kishechnogo trakta (klinicheskie nablyudeniya).

The incidence of intestinal fistulas after laparotomy for various reasons (peritonitis, acute pancreatitis or trauma) is 1.5%. Fistula formation in patients with chronic gastrointestinal diseases has a rapid onset, severe course, and poor prognosis. Against the background of a long course of the disease and depletion of the body, there is a decrease in the activity of reparative processes, which leads to the manifestation of postoperative complications: the formation of fistulas, insolvency of intestinal anastomoses, peritonitis. Vacuum drainage is a treatment method aimed at eliminating exudate, reducing the area of the wound and its epithelization. The inclusion of a succinate-containing solution in the treatment regimen improves metabolic processes and improves the prognosis of the disease. As an illustration, a description of the clinical observation of patients with similar pathology and different treatment regimens is given.

[Caroli disease: optimizing the choice of surgical strategy using 3D modeling, 3D printing and therapy]. / Bolezn' Karoli: optimizatsiya vybora khirurgicheskoi taktiki s ispol'zovaniem 3D-modelirovaniya, 3D-pechati i terapii.

A patient with Caroli disease is described. The authors used 3D modeling and 3D printing when choosing surgical strategy. Advisability of 1.5% meglumine sodium succinate 500 ml IV once a day (courses for 5 and 8 days) is justified. Thanks to antihypoxic mechanism, this drug reduced intoxication syndrome and length of hospital-stay, as well as improved quality of life.

[3D-modelling and 3D-printing in diagnosis and treatment of common bile duct stricture]. / Opyt primeneniya 3D-modelirovaniya i 3D-pechati pri diagnostike i vybore metoda lecheniya striktury gepatikokholedokha.

An example of the use of 3D-modeling of 3D-printing in the diagnosis and choice of a surgical approach for the treatment of hepaticocholedochal stricture is given. The inclusion of meglumine sodium succinate (intravenous drip, once a day, 500 ml, course of 10 days) into the therapy regimen was substantiated, which contributed to the reduction of intoxication syndrome due to its antihypoxic mechanism of action and, as a result, to a reduction in the duration of hospitalization and an increase in the quality of life of the patient.