Bilateral symmetrical lipoma of the buccal fat pad as an incidental finding in a woman with weight gain after tamoxifen: a case report

Although lipoma is a common benign tumor, it occurs relatively infrequently in the oral and maxillofacial areas, and only 31 cases of lipoma in the buccal fat pad have been reported. Herein, we present an extremely rare case of symmetric lipomas in both buccal fat pads. These masses were incidentally discovered during a facelift procedure in a 50-year-old woman with a 4-year history of tamoxifen use. during which she had gained 10 kg. The patient stated that cheek protrusion had developed concomitantly with weight gain and was exacerbated by an injection lipolysis procedure she had received 1 year previously. This case underscores the importance of paying careful attention to the patient’s medication use and surgical history when evaluating suspected cases of lipoma, and sheds light on tamoxifen use and subcutaneous injections of phosphatidylcholine and deoxycholate as potential risk factors for lipoma development.

Allosteric Modulation of NMDARs Reverses Patients' Autoantibody Effects in Mice

Background and ObjectivesTo demonstrate that an analog (SGE-301) of a brain-derived cholesterol metabolite, 24(S)-hydroxycholesterol, which is a selective positive allosteric modulator (PAM) of NMDA receptors (NMDARs), is able to reverse the memory and synaptic alterations caused by CSF from patients with anti-NMDAR encephalitis in an animal model of passive transfer of antibodies.MethodsFour groups of mice received (days 1–14) patients' or controls' CSF via osmotic pumps connected to the cerebroventricular system and from day 11 were treated with daily subcutaneous injections of SGE-301 or vehicle (no drug). Visuospatial memory, locomotor activity (LA), synaptic NMDAR cluster density, hippocampal long-term potentiation (LTP), and paired-pulse facilitation (PPF) were assessed on days 10, 13, 18, and 26 using reported techniques.ResultsOn day 10, mice infused with patients' CSF, but not controls' CSF, presented a significant visuospatial memory deficit, reduction of NMDAR clusters, and impairment of LTP, whereas LA and PPF were unaffected. These alterations persisted until day 18, the time of maximal deficits in this model. In contrast, mice that received patients' CSF but from day 11 were treated with SGE-301 showed memory recovery (day 13), and on day 18, all paradigms (memory, NMDAR clusters, and LTP) had reversed to values similar to those of controls. On day 26, no differences were observed among experimental groups.DiscussionAn oxysterol biology-based PAM of NMDARs is able to reverse the synaptic and memory deficits caused by CSF from patients with anti-NMDAR encephalitis. These findings suggest a novel adjuvant treatment approach that deserves future clinical evaluation.

CRISPR Gene Editing in Lipid Disorders and Atherosclerosis: Mechanisms and Opportunities

Elevated circulating concentrations of low-density lipoprotein cholesterol (LDL-C) have been conclusively demonstrated in epidemiological and intervention studies to be causally associated with the development of atherosclerotic cardiovascular disease. Enormous advances in LDL-C reduction have been achieved through the use of statins, and in recent years, through drugs targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of the hepatic LDL-receptor. Existing approaches to PCSK9 targeting have used monoclonal antibodies or RNA interference. Although these approaches do not require daily dosing, as statins do, repeated subcutaneous injections are nevertheless necessary to maintain effectiveness over time. Recent experimental studies suggest that clustered regularly interspaced short palindromic repeats (CRISPR) gene-editing targeted at PCSK9 may represent a promising tool to achieve the elusive goal of a ‘fire and forget’ lifelong approach to LDL-C reduction. This paper will provide an overview of CRISPR technology, with a particular focus on recent studies with relevance to its potential use in atherosclerotic cardiovascular disease.

Experience of therapy of psoriasis patients with methotrexate in the form of subcutaneous and intramuscularly injections

Псориаз является одним из наиболее распространенных хронических дерматозов, в мире зарегистрировано около 125 млн больных этим заболеванием, причем частота встречаемости в структуре дерматологических заболеваний составляет около 40%. Несмотря на то, что в большинстве случаев псориаз не представляет угрозы для жизни, тем не менее он является непосредственной причиной появления весьма серьезных патологических проблем, социальной дезадаптации. В последнее время все большее число исследователей говорят о псориазе не как об изолированном кожном заболевании, а как о системной псориатической болезни с доминирующими проявлениями на коже. Системность заболевания проявляется в частом вовлечении в процесс не только кожного покрова, но и других систем и органов, в частности опорно-двигательного аппарата при артропатической форме псориаза (псориатическом артрите). Распространенность псориатического артрита у больных псориазом колеблется от 7% до 47%, причем у 15% пациентов артрит развивается до поражения кожи, при обычном псориазе артрит бывает в 6-7% случаев, а при уже выявленной псориатической артропатии у 73,2% больных встречается пустулезный или экссудативный псориаз, а также псориатическая эритродермия. В статье представлены результаты применения в терапии больных среднетяжелым и тяжелым псориазом препарата метотрексат в виде подкожных инъекций в сравнении с аналогичной схемой использования внутримышечных инъекций метотрексата. Показана высокая эффективность курса терапии метотрексатом в лечении псориаза и псориатического артрита. Приведены данные о более высокой безопасности, более значимом позитивном влиянии на качество жизни, о лучшей переносимости и более длительной ремиссии, достигнутых в группе пациентов, получавших подкожные инъекции метотрексата. Psoriasis is one of the most common chronic dermatoses. About 125 million patients with this disease are registered in the world, and the frequency of occurrence in the structure of dermatological diseases is about 40%. Despite the fact that in most cases psoriasis does not pose a threat to life, but, nevertheless, it is the direct cause of the appearance of very serious pathological problems, social maladjustment. Recently, an increasing number of researchers speak of psoriasis not as an isolated skin disease, but as a systemic psoriatic disease with dominant skin manifestations. The systemic nature of the disease is manifested in the frequent involvement in the process of not only the skin, but also other systems and organs, in particular, the musculoskeletal system in the arthropathic form of psoriasis (psoriatic arthritis). The prevalence of psoriatic arthritis in patients with psoriasis ranges from 7 to 47%, and in 15% of patients arthritis develops before skin lesions, with ordinary psoriasis, arthritis occurs in 6-7% of cases, and with already identified psoriatic arthropathy in 73,2%, pustular or exudative psoriasis, as well as psoriatic erythroderma. The article presents the results of the use of methotrexate in the form of subcutaneous injections in clinical practice in the treatment of patients with moderate and severe psoriasis, in comparison with a similar scheme of using intramuscular injections of methotrexate. The course of methotrexate therapy has been shown to be highly effective in the treatment of psoriasis and psoriatic arthritis. The data on higher safety, a more significant positive effect on the quality of life, better tolerability and longer remission of the process achieved in a group of patients receiving subcutaneous injections of methotrexate are presented.

Wnt/β-Catenin Pathway in Experimental Model of Fibromyalgia: Role of Hidrox®

Fibromyalgia (FM) is a chronic condition characterized by persistent widespread pain that negatively affects the quality of life of patients. The WNT/β-catenin signaling pathway seems to be involved in central sensitization and different pain states. The objective of this study was to investigate the beneficial effects of a new compound called Hidrox® (HD), containing 40–50% hydroxytyrosol, in counteracting the pain associated with FM. An FM-like model was induced in rats by subcutaneous injections of reserpine (1 mg/kg) for three consecutive days. Later, HD (10 mg/kg) was administered orally to the animals for seven days. Reserpine injections induced WNT/β-catenin pathway activation, release of pro-inflammatory mediators as well as a significant increase in oxidative stress. Daily treatment with HD was able to modulate the WNT/β-catenin and Nrf2 pathways and consequently attenuate the behavioral deficits and microglia activation induced by reserpine injection. These results indicate that nutritional consumption of HD can be considered as a new therapeutic approach for human FM.

NORMOTENSIVE RATS WITH PCOS EXHIBIT THE HYPERTENSIVE PATTERN: FOCUS ON OXIDATIVE STRESS

Numerous evidence implies complex interrelations between polycystic ovary syndrome (PCOS) and hypertension (HT) in reproductive-age women. We aimed to investigate the potential strain differences in ovarian morphology, hemodynamic and biochemical characteristics in an androgen-induced PCOS rat model. A total of 3 weeks old 24 rats (12 Wistar Kyoto - WK and 12 Spontaneously Hypertensive Rats – SHR) were divided into four groups: WK, WK PCOS, SHR, and SHR PCOS. PCOS was induced by daily subcutaneous injections of testosterone-enanthate (1 mg/100 g body weight (BW)) administered for 5 weeks. PCOS induction led to estrus cyclicity cessation, cystic ovarian appearance, and sex hormones disturbances in both strains. The morphometric parameters in ovaries were altered in a manner of PCOS-related changes in both strains (higher number in preantral, atretic and cystic follicles). Ultrasonographycally, a significant decrease in ovarian volume (OV) was registered in PCOS groups, but also in SHR compared to WK rats. All blood pressure parameters were higher in SHR compared to WK. PCOS modeling increased systolic, mean arterial and pulse pressure in WK strain, while in SHR, only mean arterial and pulse pressure were higher. Alterations in oxidative stress parameters could provide a molecular basis for PCOS-related changes: in PCOS groups, TBARS and O2- were higher in both strains, while SOD and GSH were significantly lowered.

Teriparatide Administration By The Omnipod Pump: A Self-Managed Therapeutic Option for Refractory Hypoparathyroidism

Context : Hypoparathyroidism (hypoPTH) in adults is mainly due to total thyroidectomy. Conventional therapies (calcium, active vitamin D) can fail to normalize calcemia, expose the patient to hypercalciuria and impact quality-of-life. Human parathormone (hPTH) replacement therapy is a suitable option in these cases, although few clinical reports have been published so far. Methods we describe two cases of refractory postsurgical hypoPTH for which subcutaneous infusion of recombinant parathormone (teriparatide) through the Omnipod® pump was started after failure of all other therapeutic options. Besides, we performed a review of literature of hypoPTH cases treated by continuous infusion of teriparatide. Results two women aged 46 and 61yo failed to normalize calcemia either with conventional treatments (calcium 8g/d + calcitriol 9µg/d and calcium 5g/d + calcitriol 12µg/d) or with thrice-daily subcutaneous injections of teriparatide. As a last resort, teriparatide infusion via Omnipod® device normalized their calcemia and allowed calcium/vitamin D withdrawal, with average teriparatide dose of 23 and 32 µg/day, respectively. Notably, a dedicated protocol currently allow each patient to be autonomous with its pump without adverse dyscalcemia until now. In the literature, 15 adult cases (13 women, mean age 44.5 ± 5.2 yo) are reported. HypoPTH was consecutive to surgery in all of them. Mean dose of teriparatide administered was 25 ± 6 µg/d with improvement of calcemia level and quality-of-life in all patients. Conclusion Continuous administration of teriparatide through Omnipod® is a safe and efficient therapeutic option in refractory hypoPTH, which can, furthermore, be safely self-managed by the patient.

Nandrolone Decanoate supplementation promotes AMPK activation and divergent brain connectivity rearrangements in adult and aged mice.

Abnormalities in energetic and proteic homeostasis during ageing relate to neurodegenerative diseases. The mitochondria are a hub of oxidative metabolism, influencing autophagic flux. Ageing can lead to a functional disruption of these systems, leading to neuroenergetic and proteotoxic imbalance. Lower levels of testosterone have been proposed as a mechanism accelerating functional decline during ageing. In this study we investigated whether nandrolone decanoate (ND), an analog of testosterone, in aged animals improves mitochondrial bioenergetics and autophagy. Albino CF1 mice of 3 and 18 months of age, were separated in 4 groups that received daily subcutaneous injections for 15 days of either ND (15mg/kg), or vehicle. Were performed baseline and 14th day 18FDG uptake analysis, through positron emission tomography scan. High resolution respirometry was performed to assess functionally mitochondrial respiratory states and respiratory control ratio (RCR) in synaptossomes fractions. Also, hypothalamic immunocontent of AMPK, pAMPKT172, Beclin-1 and BCL-2 LC3 was assessed. Results demonstrate that aged animals did not display alterations nor in 18FDG uptake, neither in mitochondrial respiratory states. Also, aged mice displayed reduced pAMPKT172/ AMPK ratio, and increased LC3-II compared to adult controls. Curiously, ND in aged mice did neither increase 18FDG uptake, nor alter mitochondrial states. Albeit, ND increased pAMPKT172/ AMPK ratio, LC3-II turnover, as well as increased RCR. This suggest that ageing does not culminate necessarily in bioenergetics alterations in brain, although biomarkers of energetic status and autophagy are reduced. ND improved bioenergetic efficiency and autophagy in aged mice. These benefits are probably mediated by reprogramation of AMPK signalling.