Development of State-of-the-art Experimental Technique to Investigate Temperature Field in Leakage Flows of Positive Displacement Machines

Investigation of leakage flows in oil-free rotary positive displacement machines (PDMs) is necessary to get a real insight into attributes of leakage flows. Experimental study of heat transfer in the leakage flows of the oil-free positive displacement machines is challenging. The primary reason is complexities associated with actual machine running condition such as extremely small (micron-size) clearance gap, high speed of rotors, optical access of flows etc. Therefore, this studypresents the development of state-of-the-art experimentalsetup usingPlanar La ser-Induced Fluorescence (PLIF) technique to visualize the temperature field in the clearance flows of rotary machines. This study considers Roots blower to implement PLIF technique because it provides relatively easy optical access. Besides, it is a good representative of PDMs. Selection criteria of optical glass, suitable tracer particles, Imaging camera, optical lenses and filters are investigated in detail. Pixel Intensity was found to be conformable in the clearance gap from recorded images of temperature field, thereby confirmed the efficacy of the flow visualization and instrumentation systemsdeveloped

Case series of mucormycosis occurring in patients of COVID-19

Mucormycosis is an umbrella term used for diseases caused by many non-septate filamentous fungal species which is caused by sub-phylum Mucormycotina. It is an acute opportunistic and aggressive fulminant invasive infection that can occur in immunocompromised patients, such as uncontrolled diabetes, renal failure, organ transplant, long-term corticosteroid and immunosuppressive therapy, AIDS, malignancy and corona virus disease 2019 (COVID 19) infections. Mucormycosis is now third most common invasive mycoses after candidiasis and aspergillosis. The COVID-19 infection is characterised by wide range of disease patterns, ranging from mild to life-threatening pneumonia. Many bacterial and fungal co-infections may exist and may be associated with preexisting morbidity or may develop as a hospital-acquired infection such as ventilator-associated pneumonia. Extensive use of corticosteroids and broad-spectrum antibiotics lead to exacerbation of preexisting disease. The aim of this study is to identify the risk factors along with high index of suspicion, early diagnosis and aggressive management of mucormycosis

Exploring the mechanistic pathway of various phosphodiesterase inhibitors in airway smooth muscle cells

Asthma is a chronic lung disease with complex inflammatory disorder. In asthma, airways are remodelled and narrowed, resulting into increased mucus production and contraction of muscles. It has been known that in asthma, airway smooth muscle (ASM) cells act as the primary effector and pivotal cell type involved in asthma. The current treatment suggests β2-agonists as drugs of choice for bronchodilation in ASM cells and long acting β2-agonists (LABA) combined with inhaled corticosteroid (ICS) are used as maintenance therapy in asthma. The mechanism of β2-agonists works via increased levels of cyclic adenosine mono phosphate (cAMP) in ASM cells. It is well established that a rapid increase in cAMP levels in ASM are critical for effective bronchial relaxation however, these intracellular cAMP levels is labile and reduced by phosphodiesterase (PDEs) enzymes. PDEs are intracellular regulators catalysing the breakdown of cAMP and/ cGMP (cyclic guanosine-5'-monophosphate) to their inactive forms. This makes β2-agonists less effective in relaxation of bronchial muscles. The molecular mechanism of PDE is still not clearly known and there are no approved PDE inhibitors in the market for asthma. Our hypothesis is that once we treat ASM cells with PDE inhibitors in addition to LABA and corticosteroid, the effectiveness of LABA and corticosteroid will enhance in airway inflammation. In addition to the bronchial relaxation effect of β2-agonists, also causes anti-inflammatory properties due, in part, to their ability to upregulate mitogen-activated protein kinase phosphatase 1 (MKP-1) in a cAMP-dependant manner. Given that MKP-1 is cAMP-dependant and inhibition of PDE acts to increase β2-agonist-induced cAMP, it is possible that the presence of PDE inhibitors may enhance β2-adrenoceptor-mediated responses. Additionally, it would enable us to understand the molecular mechanism of these PDE inhibitors as a possible additive therapy for asthma in the future. Among all PDE isoenzymes inhibition of PDE3 and PDE4 are the main targets for ASM cells. Utilizing primary cultures of ASM cells, we showed in chapter 3 that inhibitors of PDE4, but not PDE3, increase β2-agonist-induced cAMP, MKP-1 mRNA and protein upregulation. When cAMP was increased there was a concomitant increase in MKP-1 levels and significant inhibition of tissue necrosis factor α (TNFa) induced neutrophil chemoattractant cytokine, interleukin -8 (IL-8). This result was consistent with all PDE4 inhibitors examined but not for the PDE3 inhibitors. These findings reinforce cAMP-dependent control of MKP-1 expression in ASM cells. Since MKP-1 is an integral part of the anti-inflammatory effect of PDE4 inhibitors in ASM cells, we were keen to see the effect of a newer generation of PDE4 inhibitor, Roflumilast N-oxide (RNO) for anti-inflammatory repression. RNO is approved for use in chronic obstructive pulmonary disease (COPD) and has demonstrated anti-inflammatory impact in vivo and in vitro. Up to the present time, however, the effect of RNO on the synthetic function of ASM cells is unknown. We address this herein in chapter 6 and investigate the effect of RNO on β2-adrenoceptor-mediated, cAMP-dependent responses in ASM cells in vitro, and whether RNO enhances steroid-induced repression of inflammation. RNO (0.001-1000 nM) alone had no effect on cAMP production from ASM cells, and significant potentiation of the formoterol-induced cAMP could only be achieved at the highest concentration of RNO tested (1000 nM). At this concentration, RNO exerted a small, but not significantly different, potentiation of formoterol-induced expression of anti-inflammatory MKP-1. Consequently, TNFα induced IL-8 secretion was unaffected by RNO in combination with formoterol. However, as there was the potential for PDE4 inhibitors and LABA to interact with corticosteroids to achieve superior anti-inflammatory efficacy, we examined whether RNO, alone or in combination with formoterol, enhanced the anti-inflammatory effect of dexamethasone. While RNO alone did not significantly enhance cytokine repression achieved with steroids, RNO in combination with formoterol significantly enhanced the anti-inflammatory effect of dexamethasone in ASM cells. Once we had obtained reliable results from the PDE4 inhibitors we were intrigued to investigate the molecular mechanism of non-specific PDE inhibitors, mainly xanthine derivatives such as theophylline and doxophylline, for their formoterol-induced cAMP effect in ASM cells. We showed in chapter 4 and 5 that theophylline and doxophylline both did not potentiate cAMP release from ASM cells treated with formoterol. Moreover, theophylline (0.1-10 µM) did not increase formoterol-induced MKP-1 mRNA expression nor protein upregulation; consistent with the lack of cAMP generation. Similar trends observed for doxophylline (0.1-100 µM) where cAMP level was not enhanced. In asthma, adenosine receptor activates adenylate cylclase which leads to elevation of cAMP however doxophylline have lower affinity for adenosine receptor so does not induce cAMP. Theophylline (at 10 µM) was anti-inflammatory and repressed secretion of IL-8, produced in response to TNFa. Because theophylline’s effects were independent of PDE4 inhibition or anti-inflammatory MKP-1, we then wished to elucidate the novel mechanisms responsible. We investigated the impact of theophylline on protein phosphatase 2A (PP2A), a master controller of multiple inflammatory signalling pathways, and showed that theophylline increases TNFa induced PP2A activity in ASM cells. In spite of positive clinical data for doxophylline with exhibition of lesser side effects in recent studies, our results do not appear to have any significant repression of IL-8 in ASM cells. Further experiments with less variability in the results and tight control on cell plating techniques may provide better understanding of results and test our hypothesis more fully. Overall our study suggests that understanding the molecular mechanism of various PDE inhibitors in ASM cells offers an additive option as anti-inflammatory therapy in asthma

Effects of a New Topical Treatment Containing Several Hair Growth Promoters in Women with Early Female Pattern Hair Loss

Female pattern hair loss (FPHL) is increasing ly common and often presents with hair shedding. Spec tral. DNC-N® contains anti-inflammatory actives and hair growth promoters. To assess the efficacy and tolerability of Spectral DNC-N® (DS Laboratories, Inc.) in women with early FPHL and excessive shedding. Forty-nine patients were treated with Spectral DNC-N®, applied twice daily for 3 months; 28 patients were included in the 3-month treatment extension. Efficacy assessments included the degree of hair shedding using the validated hair shedding visual scale, hair mass index (HMI), and photographic evaluation. There was a statistically significant decrease in hair shedding and a corresponding increase in HMI by month 3, which was maintained through month 6. The mean investigator-assessed hair shedding score decreased from 3.5 to 2.0 and the hair mass increased from 75.8 to 84.3 mm>sup /sup sup /sup< by month 3 (both < 0.01 compared with baseline). By month 6, the hair shedding score was reduced to 1.6 and the hair mass was maintained. Most patients (75%) showed an increase in global hair density. Spectral. DNC-N® significantly reduced hair shedding, with a corresponding increase in hair mass and density. These effects were already evident after 3 months' treatment and further improved in those patients who continued treatment to month 6. Tolerability was good and patient satisfaction levels were high