AMM 2024, Volume 70 Number 2
Keywords:
Author Archives: administrare
The effects of pearl oyster shell-derived bone grafts on TNF-alfa levels: An in vivo study in Cavia porcellus
DOI: 10.2478/amma-2024-0015
Objective: This study aims to assess the effect of bone graft materials derived from pearl oyster shells on the tumor necrosis factor-alpha (TNF-α) level.
Methods: This research utilized a bone graft containing hydroxyapatite Pinctada maxima (HPM) powder obtained from pearl oyster shells. Material testing was conducted on 30 male guinea pigs aged 8-10 weeks, divided into three groups: the negative control group, the group treated solely with HPM, and the group treated with HPM combined with platelet-rich fibrin (PRF). Each treatment group was observed for 7 and 14 days. The results were analyzed using One-way ANOVA with a significance level of p<0.05.
Results: The findings demonstrated a decrease in the average TNF-α levels across all groups. On observation days 7 and 14, the HPM group exhibited a significant difference compared to the negative control group, indicating reduced TNF-α levels. However, no significant difference was observed when comparing the HPM group with the HPM and PRF groups.
Conclusions: Bone grafts derived from pearl oyster shells possess high levels of hydroxyapatite, and the addition of PRF into the bone graft effectively reduces TNF-α.
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Exploring the impact of high shear mixing process parameters on the physical characteristics of excipient powder blend by design of experiments
DOI: 10.2478/amma-2024-0016
Objective: Dry-route manufacturing technology development poses challenges to pharmaceutical technology research specialists, relying on active substance characteristics, excipient selection, and parameter optimization. Amongst various technological possibilities high shear mixing generally ensures dosage uniformity and tablet dissolution through influential shear forces, potentially enhancing dry powder blend processability. This study explores the processability of a placebo formulation within the quality by design framework to address some of the aforementioned challenges.
Methods: A 2^4 full-factorial experimental design was used to assess the manufacturability of a placebo formulation via high shear mixing. The effect of impeller and chopper speed, high shear mixing time, and homogenization/lubrication times on powder blend rheology and compression properties was investigated.
Results: The findings of the present study showed that product critical quality attributes like resistance to crushing or disintegration time are mainly dependent on the mixing efficiency translated by the impeller speed and high shear mixing time. Software augmented process development enabled the attainment of the design space, ensuring the fulfilment of desired product performance criteria. Furthermore, the study has also shown that the careful selection of excipients is crucial in the case of dry-route manufacturing technologies, as sodium lauryl sulphate can noticeably influence the processability of powder blends due to its lubricant properties.
Conclusions: Considering the advantages and challenges raised by high-shear mixing, software aided data analysis can further augment the formulation, scale-up and lifecycle management of products developed using this technological process.
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The gut-skin axis: Investigating gut microbiota
dysbiosis in pemphigus and bullous pemphigoid
DOI: 10.2478/amma-2024-0017
Gut microbiota dysbiosis has been linked with numerous autoimmune disorders and inflammatory skin pathologies. The present study is a narrative review aiming to examine dysregulations in the gut microbiota of patients with pemphigus and bullous pemphigoid, exploring how these alterations may contribute to diseases’ development and/or progression. Significant alterations in the composition of intestinal microbiota were identified in patients with pemphigus and bullous pemphigoid: reduction in short-chain fatty acid-producing bacteria: Faecalibacterium prausnitzii, Lachnospiraceae and Coprococcus spp., which are known for their anti-inflammatory effects, and increased abundance of Escherichia coli, Shigella spp., Klebsiella spp., Bacteroides fragilis and Flavonifractor spp., which are recognized for their pro-inflammatory impact. The composition of gut microbiota might influence the pathogenesis of autoimmune bullous diseases. Modified levels of bacteria could become innovative biomarkers for the detection of high-risk individuals, monitoring disease progression and predicting response to treatment. Furthermore, regulating bacterial levels might have therapeutic effects in diminishing inflammation and disease advancement, potentially serving as future therapeutic strategies.
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Beyond the gut – Atypical presentation of Salmonella spp. infection
DOI: 10.2478/amma-2024-0014
Salmonella is a Gram-negative, non-spore-forming, motile, facultative anaerobic rod. The most studied species are Salmonella typhi and paratyphi (causing typhoid fever) and non-typhi Salmonella species (which can cause different clinical syndromes – gastroenteritis, disseminated infections, etc.). A 61-year-old male patient with multiple comorbidities (including myelofibrosis) presented to the Pulmonology outpatient department, Clinical County Hospital of Târgu Mureș, with a mucopurulent nocturnal cough. Paraclinical examinations showed the presence of a pleural empyema, which was evacuated in local anesthesia. The pleural fluid was sent to the Microbiology Department for bacteriological testing, where a fluoroquinolone-resistant strain of Salmonella spp. was detected. The patient received antibiotic treatment according to the antibiotic susceptibility testing. Due to the persistence of the symptoms, the patient returned two weeks later, when another puncture was performed. Salmonella was isolated again, but the strain showed a higher resistance to antibiotics. The two strains were compared using molecular methods of diagnosis (Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction – ERIC-PCR), the results showing a similarity of 92%. The occurrence of an extra amplicon band in ERIC-PCR suggests an important change in the bacterial genetic material, potentially related to acquisition of antibiotic resistance factors.
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Prognostic value of leukocyte-glycemic index in long-term evolution of diabetic patients with peripheral arterial disease following endovascular treatment
DOI: 10.2478/amma-2024-0013
Objective: The aim of this article is to determine the predictive value of the leukocyte-glycemic index in the long-term evolution of diabetic patients with peripheral arterial disease following endovascular treatment.
Methods: This retrospective observational study enrolled 127 diabetic patients diagnosed with peripheral arterial disease requiring endovascular treatment. Patients were categorized into two groups based on the severity of the infrapopliteal atherosclerotic lesions identified during the pre-operative Computer Tomography Angiography examination. Group 1 includes patients without severe damage to the infrapopliteal artery, while Group 2 includes patients with severe infrapopliteal artery damage, identified by stenosis greater than 70% on all infrapopliteal arteries. The primary outcome was to assess the association between leukocyte-glycemic index value at baseline and the severity of infrapopliteal atherosclerotic lesions and long-term major amputation after percutaneous transluminal angioplasty.
Results: Patients in Group 2 had a higher incidence of cardiovascular events (p=0.009), stage IV Leriche-Fontaine (p=0.016), and incidence of major amputation (p<0.001), as well as an increased value of leukocyte-glycemic index (p=0.004). During the follow-up, patients with above-median leukocyte-glycemic index value have a higher risk of major amputation (p=0.034), as seen in the Kaplan-Meier analysis. Moreover, at cox-regression, elevated biomarker values were associated with long-term risk of major amputation, independent of age, sex, cardiovascular risk factors, and below-the-knee arterial occlusion (HR:2.69, p=0.001).
Conclusions: Elevated values of leukocyte-glycemic index are associated with the severity of infrapopliteal atherosclerotic lesions and major amputation in the long term.
Keywords: peripheral arterial disease, leukocyte-glycemic index, endovascular treatment, vascular surgery
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Cannabidiol, a promising therapy for post-traumatic stress disorder and depression. A mini-review
DOI: 10.2478/amma-2024-0012
Post-traumatic stress disorder (PTSD) is a mental health disorder, manifesting in people who have endured traumatic events like violence, war, natural disasters, accidents, or other life-threatening situations. Essentially, PTSD is a chronic and debilitating disorder, significantly impacting mental health and psychosocial well-being, necessitating the exploration of novel treatment approaches. Although conventional therapies like psychotherapy and antidepressants have demonstrated efficacy for certain individuals, their effectiveness is limited for some and minimal for others. Consequently, researchers and clinicians are investigating alternative therapeutic methods for these conditions. Among these emerging treatments, cannabidiol (CBD) has shown promising results. Nevertheless, early studies suggest that CBD might yield positive outcomes in mitigating symptoms related to both depression and PTSD.
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Ex vivo permeability study and in vitro solubility characterization of oral Canagliflozin self-nanomicellizing solid dispersion using Soluplus® as a nanocarrier
DOI: 10.2478/amma-2024-0011
Background and objective: Self-nanomicellizing solid dispersion SNMSD is a new formulation that combines solid dispersion and nanomicelle strategies; the strategy involves utilizing a suitable carrier that self-assembles into nanomicelles when interacting with gastrointestinal fluids. Canagliflozin, a sodium-glucose cotransporter-2 inhibitor for treating type 2 diabetes, has been linked to poor absorption due to its insolubility in aqueous media. The study aimed to create self-nanomicellizing solid dispersion systems for canagliflozin to overcome its pharmaceutical limitations and improve oral bioavailability.
Materials and Methods: Soluplus® was chosen as a nanocarrier to improve canagliflozin solubility after screening several polymers using a phase solubility study. The solvent evaporation method was selected for preparing the solid dispersion. The optimal formula was characterized through ex vivo permeability and in vitro studies.
Results: The CFZ-SNMSD formula, with a particle size PS of 60.77±1.00 nm and polydispersity index PDI of 0.06±0.02, has a stable distribution upon dilution to 20-fold with water. The apparent solubility of canagliflozin in the optimized CFZ-SNMSD formula was enhanced by 904.40±4 folds due to amorphization and nanomicellization, as demonstrated by transmission electron microscopy. CFZ-SNMSD formula showed a significant enhancement in dissolution rate compared to the physical mixture and pure drugs. The dissolution efficiency parameter confirms these findings (DE30, CFZ-SNMSD = 77.20% compared to DE30, pure drug = 18.28%). Studies show that canagliflozin’s permeability increases exponentially over time due to Soluplus® dispersibility, solubilization, and glycoprotein inhibitory effect, enhancing bioavailability and overcoming GIT membrane barriers.
Conclusions: The study indicates that canagliflozin self-nanomicellizing solid dispersion systems are promising methods for improving the oral bioavailability of canagliflozin medication.
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Beneficial effects of Anemone palmata extracts on male rabbit fertility and reproduction
DOI: 10.2478/amma-2024-0010
Objective: The current study is intended to offer an insight on positive benefits of the herb Anemone palmate belonging to Ranunculaceae family, as an enhancing agent of male rabbit’s fertility.
Methods: Twelve male rabbits, in the growth stage, were divided randomly into four equal groups: one serving as the control and three subjected to different treatments. Anemone palmata extracts (50, 100, and 200 mg/kg) were administered orally to the groups. Blood samples were collected to measure the serum levels of testosterone four weeks later. The weight of the testis and epididymis, sperm count, and sperm motility were determined histologically.
Results: The findings revealed a significant increase in the relative weights of the reproductive organs (testis and epididymis) and plasma testosterone levels in the groups that received the 100 and 200 mg/kg doses. Moreover a notable enhancement in the spermatozoa biology, including concentration, motility, and speed, was observed in the groups treated with 100 and 200 mg/kg doses compared to the control and the group treated with 50mg/kg. The histological study revealed some changes in the spermatogenesis and the structure of the organs, involving the presence of the spermatid phase. A significant increase in the thickness of seminiferous walls, a decrease in the interstitial space, and a reduction in the lumen and intra-tubular spaces were observed as well.
Conclusions: it is well indicated that Anemone palmata could improve fertility factors, and exhibit good effects on gonad and sperm parameters in rabbits.
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Assessing the control of the disease on current treatments available in Romania for hereditary angioedema patients
DOI: 10.2478/amma-2024-0009
Background: Acute treatment must be permanently accessible for every patient diagnosed with hereditary angioedema (HAE). In many cases this type of therapy does not provide/offer sufficient control of the disease, so long-term prophylaxis (LTP) is recommended. In the case of regular and prolonged/extended administration of drugs, the route of administration is essential. The aim of the investigation was to assess the control of HAE among patients in Romania receiving the available medications, while also examining potential correlations within the outcomes.
Material and methods: A phone call was made to all adult patients registered in the Romanian HAE Registry. Patients with confirmed diagnosis of HAE who had at least one angioedema attack in the last three months were asked to complete, online, the angioedema control test (AECT) for one- and three months respectively. AECT scores were calculated according to the authors’ instructions.
Results: A total of 121 patients were contacted. Of these, 83 complies with the eligibility criteria and 56 completed the questionnaires (response rate 67.4%), 18 (32.1%) men and 38 (67.9%) women. Acute, home administered treatment with Icatibant or pdC1-INH was available for every patient during the study time. Nine (14.5%) participants used LTP too, with pdC1-INH. These treatments ensured an adequate control of the disease in only 13 patients (21%) in case of the three-month AECT, of whom 2 used LTP. The one-month questionnaire showed a well-controlled disease in 14 patients (23%), from which only 1 was on prophylactic therapy.
Conclusion: In most Romanian HAE patients, the available drugs do not offer a proper control of the disease. Even though a first-line drug for LTP is available, its administration route by intravenous injections makes it inconvenient for many patients, highlighting the necessity for new, easy-to administer drugs for HAE patients from our country.
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