ABSTRACT
Hyperinflammation and cytokine storm has been noted as a poor prognostic factor in patients with severe pneumonia related to coronavirus disease 2019 (COVID-19). In COVID-19, pathogenic myeloid cell overactivation is found to be a vital mediator of damage to tissues, hypercoagulability, and the cytokine storm. These cytokines unselectively infiltrate various tissues, such as the lungs and heart, and nervous system. This cytokine storm can hence cause multi-organ dysfunction and life-threatening complications. Mavrilimumab is a monoclonal antibody (mAb) that may be helpful in some cases with COVID-19. During an inflammation, Granulocyte-macrophage colony-stimulating factor (GM-CSF) release is crucial to driving both innate and adaptive immune responses. The GM-CSF immune response is triggered when an antigen attaches to the host cell and induces the signaling pathway. Mavrilimumab antagonizes the action of GM-CSF and decreases the hyperinflammation associated with pneumonia in COVID-19, therefore strengthening the rationale that mavrilimumab when added to the standard protocol of treatment could improve the clinical outcomes in COVID-19 patients, specifically those patients with pneumonia. With this review paper, we aim to demonstrate the inhibitory effect of mavrilimumab on cytokine storms in patients with COVID-19 by reviewing published clinical trials and emphasize the importance of extensive future trials.
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Objective:Ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry （UHPLC-Q-Orbitrap-MS） was used to rapidly analyze and assign the chemical constituents of Naizilai granules. Method:An ACQUITY UPLC BEH Shield RP C<sub>18</sub> column （2.1 mm×100 mm， 1.7 µm） was selected for chromatographic analysis， the mobile phase was 0.1% formic acid aqueous solution （A） and acetonitrile （B） for gradient elution （0-3 min， 1%B； 3-16 min， 1%-11%B； 16-30 min， 11%-34%B； 30-37 min， 34%-52%B； 37-42 min， 52%-100%B； 42-44 min， 100%B）， flow rate was 0.3 mL·min<sup>-1</sup> and the column temperature was 35 ℃. Mass spectrometry data of Naizilai granules were collected in positive and negative ion modes， the chemical constituents of this preparation were speculated and identified according to the precise molecular weight， secondary fragmentation and other information， combined with reference substance and literature data. Result:A total of 175 compounds were identified and speculated， including 72 flavonoids， 77 organic acids， 15 sesquiterpenes， 6 coumarins and 5 other compounds. Among these identified chemical constituents， there were 154 from <italic>Artemisia rupestris</italic>， 64 from <italic>Hyssopus cuspidatus</italic>， 33 from <italic>Cordia dichotoma</italic>， 42 from <italic>Viola tianshanica</italic>， 56 from <italic>Lactuca sativa</italic>， 65 from <italic>Mentha haplocalyx</italic>， 78 from <italic>Matricaria chamomilla</italic>， 28 from <italic>Ziziphus jujuba</italic>， 7 of which were common components of these eight herbs. Conclusion:The established analytical method can realize the rapid and accurate identification of the chemical constituents in Naizilai granules， and basically covers the main constituents of each medicinal material in the formula， so as to provide a basis for improving the quality evaluation system of the preparation and lay a foundation for elucidating the pharmacodynamic mechanism.
ABSTRACT
Hyperinflammation and cytokine storm has been noted as a poor prognostic factor in patients with severe pneumonia related to coronavirus disease 2019 (COVID-19). In COVID-19, pathogenic myeloid cell overactivation is found to be a vital mediator of damage to tissues, hypercoagulability, and the cytokine storm. These cytokines unselectively infiltrate various tissues, such as the lungs and heart, and nervous system. This cytokine storm can hence cause multi-organ dysfunction and life-threatening complications. Mavrilimumab is a monoclonal antibody (mAb) that may be helpful in some cases with COVID-19. During an inflammation, Granulocyte-macrophage colony-stimulating factor (GM-CSF) release is crucial to driving both innate and adaptive immune responses. The GM-CSF immune response is triggered when an antigen attaches to the host cell and induces the signaling pathway. Mavrilimumab antagonizes the action of GM-CSF and decreases the hyperinflammation associated with pneumonia in COVID-19, therefore strengthening the rationale that mavrilimumab when added to the standard protocol of treatment could improve the clinical outcomes in COVID-19 patients, specifically those patients with pneumonia. With this review paper, we aim to demonstrate the inhibitory effect of mavrilimumab on cytokine storms in patients with COVID-19 by reviewing published clinical trials and emphasize the importance of extensive future trials.
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A 77-year-old man with a past medical history of type 2 diabetes mellitus, peripheral neuropathy, and chronic obstructive pulmonary disease was admitted to the intensive care unit of Bangladesh Medical College Hospital with acute encephalopathy and non-ST segment elevation myocardial infarction (NSTEMI). The patient was on antidiabetic medicine along with H2 blocker and multivitamins for his existing diseases. The patient’s attendant reported that the patient had received his first dose of the Moderna coronavirus disease 2019 (COVID-19) vaccine just 2 days ago. Physical examination revealed that he had a Glasgow Coma Scale of 8/15; a pulse of 106 beats/min; a respiratory rate of 30 breaths/min; oxygen saturation of 80% on room air, which became with 10 L of oxygen and blood pressure of 90/60 mm Hg at the time of admission. During the hospital stay, the patient was treated conservatively with intravenous antibiotics and other necessary medication. Although we have observed the onset of encephalopathy and NSTEMI following COVID vaccination for this patient, we, as healthcare professionals, cannot directly attribute the cause of the complications to the Moderna vaccine without further epidemiological studies with large samples.
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@#Introduction: Fluorosis has been associated with an increased risk of degenerative changes in the knee. Multiple studies have found an association between arthritis and elevated fluoride levels. We aim to delineate if elevated fluoride level has any direct correlation with the degree of radiological grading and clinical symptoms in knee arthritis. Materials and Methods: A cross-sectional study of 80 knee arthritis patients was conducted from February 2017 to April 2018. Serum fluoride levels were measured and patient’s pain scores, WOMAC scores and radiological grading were correlated with the elevated fluoride levels. Results: In our study, 30 out of 80 patients had increased serum fluoride level. Statistically significant differences were noted in VAS score, WOMAC score and Kellgren and Lawrence radiological grades between patients with normal serum fluoride level and those with elevated fluoride level. Conclusion: There is an increased risk of knee arthritis in patients with elevated blood fluoride levels and patients with increased fluoride levels are associated with more severe symptoms and radiographic disease.
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Background: Pyoderma gangrenosum is a neutrophilic dermatosis of unknown etiology, with inconstant systemic associations and a variable prognosis. Aims: To study the clinical features and systemic associations of pyoderma gangrenosum and its response to treatment. Methods: All patients diagnosed to have pyoderma gangrenosum at the dermatology department of the Government Medical College, Kozhikode, from January 01, 2005 to December 31, 2014 were included in this prospective study. Results: During the 10-year study period, 61 patients were diagnosed to have pyoderma gangrenosum. A male predilection was noted. The most common clinical type was ulcerative pyoderma gangrenosum (90.2%). More than 60% of patients had lesions confi ned to the legs; 78.7% had a single lesion and 27.9% had systemic associations. Most patients required systemic steroids. Patients with disease resistant to steroid therapy were treated with intravenous immunoglobulin G and split-thickness skin grafts under immunosuppression induced by dexamethasone pulse therapy. All except one patient attained complete disease resolution. Limitations: The main limitation of our study was the small sample size. Conclusions: The male predilection documented by us was contrary to most previous studies. We found split-thickness skin graft to be a useful option in resistant cases. More prospective studies may enable the formulation of better diagnostic criteria for pyoderma gangrenosum and improve its management.
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Rosa rugosa Thunb, a deciduous shrub of the genus Rosa, has been widely used to treat stomach aches, diarrhoea, pain, and chronic inflammatory disease in eastern Asia. In recent years, our research team has extensively studied the Rosa rugosa flower extract, and specifically undertook pharmacological experiments which have optimized the extraction process. Our methods have yielded a standard extract enriched in phenolic compounds, named PRE. Herein, we expand our efforts and evaluated the anti-inflammatory activity of PRE on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. PRE significantly inhibited production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-a, interleukin (IL)-6, and interleukin 1β (IL-1β), as well as expression of their synthesizing enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX-2). Furthermore, PRE inhibited activity of mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappa B (NF-κB) signaling pathway. Our findings are the first to explain the anti-inflammatory mechanism by PRE in LPS-stimulated macrophages. Given these results, we propose that PRE has therapeutic potential in the prevention of inflammatory disorders.
Subject(s)
Dinoprostone , Asia, Eastern , Flowers , Inflammation , Interleukins , Macrophages , Mitogen-Activated Protein Kinases , Nitric Oxide , Nitric Oxide Synthase Type II , Phenol , Rosa , Stomach , Tumor Necrosis Factor-alphaSubject(s)
Asymptomatic Diseases , Female , /analysis , Humans , Male , Syphilis/epidemiology , Syphilis/immunologyABSTRACT
Objective: To evaluate the antibacterial activity of essential oil from Trigonella foenum-graecum seeds powder, and identify the compounds from the extracted oil. Methods: The seeds powder of Trigonella foenum-graecum was subjected to Clevenger extractor. Seven strains of bacteria were used to test antibacterial activity of the extract. The activity against bacteria was tested by disk diffusion method using Whatman No. 1 filter paper. Gas chromatography mass spectrometry analysis was performed with an Agilent7890/5975B-gas chromatography/mass selective detector. Results: The hydrodistillation of seeds powder yielded 0.285%(v/w) of oil. Disk diffu-sion of the oil showed bactericidal activity against both Gram negative and Gram positive bacteria of tasted strains. The inhibition zone ranged from (8 ± 0) mm to (15.0 ± 0.7) mm depending on microbial strains. Gas chromatography mass spectrometry analysis showed 14 different compounds. The total compounds represented 80.96%of the oil. Conclusions: The antibacterial activity is due to the effects of different biological active compounds present in the extract. Identification of the compounds may help to develop new effective antimicrobial agent(s). Further researches on purification, characterization and toxicology of the active compounds are needed.
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Objective: To evaluate the antibacterial activity of essential oil from Trigonella foenum-graecum seeds powder, and identify the compounds from the extracted oil. Methods: The seeds powder of Trigonella foenum-graecum was subjected to Clevenger extractor. Seven strains of bacteria were used to test antibacterial activity of the extract. The activity against bacteria was tested by disk diffusion method using Whatman No. 1 filter paper. Gas chromatography mass spectrometry analysis was performed with an Agilent7890/5975B-gas chromatography/mass selective detector. Results: The hydrodistillation of seeds powder yielded 0.285% (v/w) of oil. Disk diffusion of the oil showed bactericidal activity against both Gram negative and Gram positive bacteria of tasted strains. The inhibition zone ranged from (8 ± 0) mm to (15.0 ± 0.7) mm depending on microbial strains. Gas chromatography mass spectrometry analysis showed 14 different compounds. The total compounds represented 80.96% of the oil. Conclusions: The antibacterial activity is due to the effects of different biological active compounds present in the extract. Identification of the compounds may help to develop new effective antimicrobial agent(s). Further researches on purification, characterization and toxicology of the active compounds are needed.
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Acardiac anomaly is a rare complication of multiple pregnancies. It is a hemodyamically disadvantaged nonviable twin which occurs in association with a twin reversed arterial perfusion sequence (TRAP). In TRAP, blood flows from an umbilical artery of the pump twin in reverse direction into umbilical artery of the perfused (or acardiac) twin via an arterial to arterial (AA) anastomosis. Its blood is poorly oxygenated and results in variable degrees of deficient development of the head, heart, and upper limb structures. The lower half of the body is usually better developed, which may be explained by the mechanism of perfusion. The pump twin is at risk of heart failure and problems related to preterm birth with a reported mortality of 50-75%. We present a case of multiple pregnancy with acardiac twin in a 26 year old lady with gestational diabetes mellitus. During ante natal check up several ultrasonographic (USG) screening showed twin pregnancy with one healthy fetus and the other fetus with inconspicuous anatomy and structure. Repeat USG at 36th week of gestation diagnosed twin pregnancy with acardiac twin. Strikingly the pump twin did not develop the usual complications and was delivered by cesarean section at 37th week of gestation.
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We present outcomes of Ahmed Glaucoma Valve [AGV] implantation in treating refractory glaucoma in a tertiary hospital in Oman. Refractory glaucoma was defined as previously failed conventional glaucoma surgery and an uncontrolled intraocular pressure [IOP] of more than 21 mmHg despite treatment with three topical and/or oral therapy. This historical cohort study was conducted in 2010. Details of medical and surgical treatment were recorded. Ophthalmologists examined eyes and performed glaucoma surgeries using AGV. The best corrected distant vision, IOP, and glaucoma medications were prospectively reviewed on 1[st] day, 1[st], 6[th], 12[th] week postoperatively, and at the last follow up. Glaucoma specialists examined and treated 40 eyes with refractory glaucoma of 39 patients [20 males + 19 females]. Neo-vascular glaucoma was present in 23 eyes. Vision before surgery was <3/60 in 21 eyes. At 12 weeks, one eye had vision better than 6/12, seven eyes had vision 6/18 to 6/60, and eight eyes had vision 6/60 to 3/60. Mean IOP was reduced from 42.9 [SD 16] to 14.2 [SD 8] and 19.1 [SD 7.8] mmHg at one and 12 weeks after surgery, respectively. At 12 weeks, five [12.5%] eyes had IOP controlled without medication. In 33 [77.5%] eyes, pressure was controlled by using one or two eye drops. The mean number of preoperative anti-glaucoma medications [2.38; SD 1.1] was reduced compared to the mean number of postoperative medications [1.92; SD 0.9] at 12 weeks. We succeeded in reducing visual disabilities and the number of anti-glaucoma medications used to treat refractory glaucoma by AGV surgery
Subject(s)
Humans , Female , Male , Cohort Studies , Treatment Outcome , Blindness , Intraocular PressureABSTRACT
Objective: This case report highlights on the challenges in the management of people with bipolar disorder. Method: We report a case of 36 year-old lady living with this disorder and her journey in a search for a meaningful life. Result: Adherence to treatment is a major determinant of outcome in bipolar patient like Ms WMY. Poor insight, negative attitudes towards treatment and poor understanding of medications and the illness can all lead to reduced adherence. Conclusion: This case demonstrates on how poverty of insight, poor social support, on-going stressors with significant life events and poor compliance to treatment create a series of stumbling blocks in recovery from bipolar disorder.
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Background: There was a recent epidemic of chikungunya (CKG) in Calicut and other northern districts of Kerala, South India, affecting thousands of people. Aims: To study the cutaneous manifestations of CKG and to have a serological and histopathological correlation. Methods: A total of 162 patients (63 males and 99 females) with cutaneous manifestations of CKG were enrolled in the study and serological confirmation was done with capture IgM ELISA for CKG. Skin biopsy was done in all representative cases. Results: Cutaneous manifestations were found more in females. There were 23 children, the youngest being 39 days old. Generalized erythematous macular rash was the most common finding. Vesicles and bullae were also common especially in infants. Localized erythema of the nose and pinnae, erythema and swelling of the pre existing scars and striae and toxic epidermal necrolysis-like lesions sparing mucosae were the other interesting findings. Different types of pigmentation were observed with a striking nose pigmentation in a large number of patients, by looking at which even a retrospective diagnosis of CKG could be made. Hence we suggest this peculiar pigmentation may be called "chik sign". There was flare up of existing dermatoses like psoriasis, lichen planus and unmasking of Hansen's disease with type 1 reaction. Serological tests were positive in 97%. Some hitherto unreported histopathologic findings like melanophages in the erythematous rashes were observed. Conclusion: A spectrum of cutaneous manifestations of CKG with a wide variety of unusual presentations with confirmed serological and histopathological evidence was encountered.
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The Fulani of northern Nigeria are indigenous semi-nomadic pastoralists whose diet consists largely of dairy products. Despite their consumption of relatively large amounts of saturated fats, an earlier study showed that their total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and serum triglyceride levels fall within the reference range of values for North Americans. Men in the cities of Jos and Abuja, two populations who also reside in northern Nigeria, differ from the Fulani with regard to diet and activity level. Males in both Jos and Abuja have diets consisting of high protein or carbohydrate and are more sedentary than the Fulani subjects. The main aims of the study were to measure the concentrations of various lipids in the blood serum of male urban dwellers in Jos and Abuja and to compare their blood lipid profiles with those of the rural Fulani (mean age 33.9 years). Blood serum samples from 118 men in Jos (mean age 37.9 years) and 77 men in Abuja (mean age 34.4 years) were analyzed for total cholesterol, triglycerides, LDL, HDL, homocysteine, folate, and vitamin B12. In addition to height and weight, systolic and diastolic blood pressures were measured. The mean total cholesterol, triglyceride, HDL and LDL values for the three groups of subjects fell within or close to the accepted range of values for North Americans. However, the Fulani males had HDL values (mean, 33.9 mg/dL) below the range of values prescribed for North Americans (>40 mg/dL). Moreover, the Fulani men and the men in Abuja had a total cholesterol/ HDL ratio of 4.2 and 4.0 respectively, which exceed the accepted value (< or =3.5) prescribed by the Columbia University. In all three populations, the incidence ofhomocysteinaemia (serum homocysteine > 12.4 micromol/L) was very high. Their mean homocysteine levels ranged from 14.7 to 16.7 pmol/L and could not be accounted for by folate or vitamin B12 status. The mean blood pressures of the Abuja (127/77 mm Hg) and the Fulani (120/74 mm Hg) men were within the normotensive range (<130/85 mm Hg). However, the mean blood pressures of the Jos males (131/85 mm Hg) indicated borderline hypertension. These data indicate that, with regard to serum lipids, urban and rural adult Nigerian males have generally favourable risk factors for cardiovascular disease when compared with healthy North Americans. All three sub-populations, however, have levels of homocysteine that are cause for concern vis-à-vis their overall health status.