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Validation of HPLC-UV method for determination of amoxicillin Trihydrate in capsule

Published on: 4th October, 2018

OCLC Number/Unique Identifier: 7877914513

The intention of the present work is to validate an easy, better and reasonable approach for estimation of amoxicillin trihydrate in tablet formulation by opposite segment(reverse phase) HPLC –UV with advanced conditions and parameters for habitual use in Rwanda well known board in pharmaceutical laboratory in order to check if no substandard or counterfeit amoxicillin has entered in our country that can result in antimicrobial resistance, treatment failure which can be a chief difficulty on public health. an easy, selective, precise, speedy, specific, and correct reverse phase HPLC UV-seen technique has been verified for the dedication of amoxicillin, in addition that is a cost-effective technique for the established method, monobasic potassium phosphate (KH2PO4) used as buffer and methanol and had been used as a mobile section in the ratio 95:5 respectively. The elution turned into finished in an isocratic mode at a go with the flow rate of 1.5ml/minute proposed method became demonstrated as according to ICH guiding principle refereeing additionally to USP necessities for amoxicillin capsule. linearity range of amoxicillin and was evaluated inside the variety of 20–160 g/ml. the correlation coefficient r2 changed into 0.9998 and the relative well known deviation between six replicates injection was always much less than 2%. The retention time was found 3.5±0.02. the high percentage of healing of amoxicillin is 100.6±4% indicates that the proposed method is exceptionally correct and precise trueness of with the trueness of 100.06±1.2% .the statistical evaluation proved that the demonstrated method is appropriate for analysis of amoxicillin as the majority drug and pharmaceutical formula with none interference from excipients .with the aid of considering the efficiency of the drug samples, all analyzed pattern were within the variety of 90-120 % of percentage of labeled amount, but the efficiency had been distinctive amongst samples. The have a look at located that no counterfeit, no substandard product turned into amongst all batches of amoxicillin samples throughout the c programming language of the look at.
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Advances in the use of GABAergic interneurons for the treatment of epilepsy

Published on: 4th September, 2019

OCLC Number/Unique Identifier: 8333008407

Forebrain GABAergic neurons, the main inhibitory type of neuron in the cortex and hippocampus, represent a highly heterogeneous cell population that has been implicated in the predisposition to epilepsy and the onset of seizure. Earlier attempts to restore inhibition and reduce seizure in animal models of epilepsy have been carried out using embryonic basal forebrain tissue as source of immature GABAergic progenitors in cell-based therapies, with promising results. For therapeutic strategies this approach appears unrealistic, while the use of pluripotent stem cells to obtain immature GABAergic neurons opens new and promising avenues. Research on neural stem cells and pluripotent stem cells has greatly advanced and protocols have been established to efficiently direct progenitor cells to differentiate towards the GABAergic lineage. However, being highly heterogeneous, these neurons are difficult to be fully represented in vitro. Better knowledge on the expressed gene profiles, at single cell level, and the differentiation trajectory of these neurons will consent a more precise monitoring of the differentiation steps. Here we review the current literature about how to obtain and characterize genuine inhibitory neurons, how these can be grafted in animal models (and one day possibly in human) and which diseases could potentially be targeted and the efficiency of therapeutic outcome. The main obstacles that need to be overcome are: a) choice of an appropriate animal model, b) availability of human cells prone to GABA differentiation, c) the full representation of all IN subtypes, their proportions and their physiological activities, d) how to monitor them on the long-term after transplant.
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The rising role of natural killer cells in patients with malignant hematological disorders and in recipients of hematopoietic stem cell transplantation

Published on: 1st October, 2019

OCLC Number/Unique Identifier: 8333010200

Natural killer (NK) cells, the third population of lymphoid cells, comprise 5%-25% of peripheral blood (PB) lymphocytes and represent the first line of defense against infections and tumors [1-7]. They can be derived from: bone marrow, PB, cryopreserved umbilical cord blood (UCB), human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), and various cell lines such as NK-92 and KHYG-1 [1]. NK cells; which have been divided into cytotoxic, tolerant, and regulatory subsets; are classified into: (1) naïve CD56 bright CD 16 dim CD 3 dim cells, (2) mature CD56 dim CD16 bright CD3 dim cells, and (3) lymphoid tissue-resident CD69+/CXCR6+ NK cells [1,2,8-11]. Although NK cells have been traditionally considered as part of the innate immune system, they have recently been shown to exhibit many of the features associated with adaptive immunity [8,12]. The functions of NK cells which are influenced by several cytokines include: elimination of infected cells, destruction of cancer cells, reducing the incidence of graft versus host disease (GVHD) following hematopoietic stem cell transplantation (HSCT), and regulation of pregnancy outcome [10,11,13]. 
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A review on the occurrence of opportunistic infections after applications of stem cell techniques

Published on: 18th December, 2019

OCLC Number/Unique Identifier: 8515595307

In recent years, stem cells technology have been used widely in basic and clinical science researches LIPUS (low-intensity pulsed ultrasound) is another technique commonly used in conjunction with stem cells that can have complications after applications. One of the important issues in using this modern technique is the occurrence of opportunistic infections and inflammatory reactions in the rejection or destruction of these cells and in turn making ineffective of its applications, which have been reviewed in the following.
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Knowledge, attitude and motivation toward stem cell transplantation and donation among Saudi population in Riyadh: Are Saudi people aware enough about the importance of stem cell transplantation and donation?

Published on: 13th November, 2020

OCLC Number/Unique Identifier: 8873218106

Objectives: The aim of this study was to assess the knowledge, attitude and motivation toward stem cell donation among Saudi population in Riyadh, Saudi Arabia. Methods: This is a cross-sectional study that was conducted at different malls in Riyadh. Selection of malls was done randomly according to the geographical distribution of Riyadh, in which sample size was calculated and distributed equally. The participants were asked to complete a questionnaire that addressed their knowledge, attitude and motivation toward stem cell transplantation and donation. Results: Results of this study showed that population knowledge about stem cell transplantation and donation is considered to be low. Only (37.8%) has enough information about stem cell transplantation and donation. There is a positive correlation between level of education and participant’s knowledge regarding stem cell transplantation and donation. The study revealed that 39.3% of participants have willingness for stem cell donation. Conclusion: It has been found that two third of population expressed lack of knowledge about stem cell transplantation and donation. Also, only 40% of participants showed willingness for donation, and the most common reason for not donating stem cell was the lack of information about stem cell and the value of donation While, increasing level of education was associated with better understanding of stem cell donation and its role in therapy and saving lives. Therefore, suitable campaign, advertising and counseling program for population is recommended to increase level of knowledge and motivation toward stem cell donation.
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Transcriptional profile of bovine preimplantation development selected based on G6PDH activity

Published on: 8th April, 2021

OCLC Number/Unique Identifier: 9026744769

The oocyte is the female gamete that contributes not only half of the genetic material but also all of the cytoplasm to the zygote, supplying the transcripts, proteins, mitochondria and other components necessary for early embryonic development. The intrinsic oocyte quality is one of the main factors affecting the embryo yield, the implantation rate and the rate of healthy offspring. It is obvious that a fertilized oocyte must reach the blastocyst stage within 6–9 days in the proper culture conditions to have a significant chance of inducing a pregnancy and producing an offspring. The ability to sustain the first week of embryonic development is clearly influenced by the follicular status from which the oocyte is obtained indicating that this developmental potential is inherent within certain oocytes. Since most early embryos that do not reach the blastocyst stage are blocked at or close to the maternal to zygotic transition (MZT)-stage, which occurs at the eight-cell stage in cattle, one could speculate that incompetent oocytes fail to appropriately activate the embryonic genome. Oocyte selection based on glucose-6-phosphate dehydrogenase (G6PDH) activity has been successfully used to differentiate between competent and incompetent bovine oocytes. Recently, molecular regulation of genes regulating biological process of Brilliant Cresyl Blue staining (BCB) selected oocytes and embryos was investigated to explain their variation in quality and developmental potentiality. This short review will highlights some of these efforts that have been done in this interesting area of research.
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The pattern of blood pressure and renal function among children with Sickle Cell Anaemia presenting in a tertiary health institution in Nigeria

Published on: 16th April, 2019

OCLC Number/Unique Identifier: 8163611724

Background: In sickle cell anemia (SCA), compromise of the renal vasculature due to sickled red cells has been recognized. Objectives: To assess the renal function and blood pressure pattern in children with sickle cell anaemia (SCA) presenting in a tertiary institution. Method: A cross-sectional study of patients with sickle cell anaemia (SCA) over six months involving the use of questionnaires, general physical examination, blood pressure, investigations for haemoglobin genotype, urinalysis, serum creatinine, screening for hepatitis B and HIV. Results: 51 children with SCA were seen. The prevalence of impaired renal function as defined by reduced eGFR <90mL/min/1.73m2 in this study was 27.5%, previous hospital admission and blood transfusion were associated with reduction in eGFR but blood pressure did not have significant correlation with the eGFR. The overall mean age at diagnosis of SCA was 4.09 ± 3.33 (years). Conclusion: Impaired renal function is a major comorbid condition in children with SCA. In countries/locations where there is no newborn screening for sickle cell disease, diagnosis is delayed, thus detecting impaired renal function may be delayed, therefore the need for early detection and management is imperative.Introduction
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Primary Cutaneous Lymphomas and Interferon Treatment

Published on: 9th January, 2017

OCLC Number/Unique Identifier: 7355942281

Primary cutaneous lymphomas (PCLs) are the second most common group of extranodal non-Hodgkin lymphomas (NHL) with an estimated annual incidence of 1/100.000. Interferons (IFNs) are used in mono or combination therapy for cutaneous lymphomas especially for cutaneous T-cell lymphomas (CTCL) for years. IFN-α is the most widely-used type for cutaneous lymphomas. IFN-α has been shown to be a highly active agent in CTCL with response rates ranging from 40% to 80%. In this review, the current information about PCLs and IFNs treatment is summarized.
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Cytomegalovirus pneumonia and Cryptogenic organizing pneumonia following pediatric stem cell transplantation for leukemia

Published on: 12th September, 2017

OCLC Number/Unique Identifier: 7355939062

Background: Knowledge of pulmonary complications (PCs) in children after hematopoetic stem cell transplantation (allo-HSCT) is limited; most data are from adult studies. Case: We describe a 8 year old girl with high risk acute myeloid leukemia who developed graft versus host disease (GVHD) on Day 20, Cytomegalovirus (CMV) pneumonia on Day 50 and Cryptogenic organizing pneumonia (COP) on Day 170 after allo-HSCT. Discussion: Cryptogenic organizing pneumonia is a rare noninfectious PCs that can be idiopathic or have several risk factors as a secondary causes, such as viral respiratory infections, drugs, GVHD and allo-HSCT. Viral respiratory infections and alloimmune lung syndromes have been reported in a few patients who have undergone transplantation. Conclusion: Transplant physicians should be kept in mind for the development of alloimmune lung syndrome in the form of COP following CMV pneumonia in patients after allo- HSCT
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Preservation of Haemostasis with Anti-thrombotic Serotonin Antagonism

Published on: 18th September, 2017

OCLC Number/Unique Identifier: 7355973980

An enquiry into the lack of attention awarded to serotonin antagonism in the treatment of arterial thrombosis revealed that the mode of action of serotonin and its platelet receptor antagonists was an action upon thrombus growth, and not, as with other anti-platelet drugs upon the initiation of thrombosis. This lack of effect could explain why this approach has been considered not to be effective. However under conditions of arterial stenosis in which there is platelet activation by increased shear stress, and during the growth phase of arterial thrombi, serotonin 5HT2A antagonism has been demonstrated to have great potentcy in dispersing thrombotic obstruction to blood flow. This mode of action, the lack of participation of serotonin in haemostasis, and the absence of serotonin in wounds accounts for the proven lack of effect of effect of pure specific 5HT2A antagonists (i.e., not those with other actions) on operative bleeding and skin bleeding times. This lack of effect on haemostasis solves the dosing problem encountered with other anti-thrombotic drugs, with which drug concentration cannot be controlled with single fixed doses, leading to the association between increased anti-thrombotic efficacy and increased bleeding complications. Thus 5HT2A antagonism appears to be the preferred approach, from the point of view of safety and lack of bleeding risk; this consideration applies particularly to thrombosis therapy in the context of traumatic accidents, surgical operations and invasive procedures such as angioplasty.
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The beneficial effects of varicella zoster virus

Published on: 15th July, 2019

OCLC Number/Unique Identifier: 8186245399

Varicella zoster virus behaves differently from other herpes viruses as it differs from them in many aspects. Recently, there has been growing evidence on the beneficial effects of the virus in immune compromised hosts and these effects are translated into prolongation of survival. The reported beneficial effects of the virus include: (1) stimulation of bone marrow activity in patients with hematologic malignancies and bone marrow failure syndromes, (2) antitumor effects in various hematologic malignancies and solid tumors, and (3) association with graft versus host disease which has anticancer effects. Additionally, there are several reports on the safety of the live-attenuated even in severely immune suppressed individuals and on the emerging role of the virus in cancer immunotherapy. In this review, the following aspects of the virus will be thoroughly discussed: (1) new data on the genetic background, pathogenesis, vaccination, and new therapeutic modalities; (2) bone marrow microenvironment and hematopoiesis; (3) cells involved in the pathogenesis of the virus such as: mesenchymal stem cells, dendritic cells, natural killer cells, T-cells and mononuclear cells; (4) cellular proteins such as open reading frames, glycoproteins, promyelocytic leukemia protein, chaperons, and SUMOs; (5) extracellular vesicles, exosomes, and micro-RNAs; and (6) signaling pathways, cytokines, and interferons.
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Hyperparathyroidism in celiac disease: A case study from UAE

Published on: 7th April, 2020

OCLC Number/Unique Identifier: 9272401475

Celiac disease affects 1% of the world population; however it is under diagnosed in UAE. The disease has many clinical manifestations, ranging from severe malabsorption to minimally symptomatic or non-symptomatic presentation. Hypocalcaemia is a common finding in celiac disease and could be the only presentation of the disease; however hypercalcemia has been previously reported in patients with celiac disease either due to primary hyperparathyroidism or tertiary hyperparathyroidism due to prolonged hypocalcaemia. A normal calcium level on the other hand in patients with untreated celiac disease who also have primary hyperparathyroidism can be due to interplay of these two conditions and may delay the diagnosis of primary Hyperparathyroidism. We report the very first case from our practice in UAE with untreated celiac disease and normal calcium level at presentation, where a diagnosis of primary hyperparathyroidism was not entertained initially. Patient went on gluten free diet which then caused normalization of intestinal abnormalities and likely calcium absorption manifesting as hypercalcemia on subsequent labs. This led to further work up and finally the diagnosis of Primary hyperparathyroidism due to parathyroid adenoma.
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Microbiome and Gastroesophageal Disease: Pathogenesis and Implications for Therapy

Published on: 21st May, 2020

OCLC Number/Unique Identifier: 8603898545

There is growing evidence that gastroesophageal disease is influenced by the esophageal microbiome, and that commensal bacteria of the oropharynx, stomach, and colon are thought to have a role in modulatiing pathogenesis. These emerging hypotheses are based on observed changes in the composition of the esophageal flora, notably, repeated observations: 1. There is an abundance of gram-positive bBacteria in the healthy esophagus. are more gram positive prevalent 2. The esophageal bacterial population becomes increasingly gram negative with disease progression. Associated with this shift to a more gram negative prevalence is an increase in the potential for the presence of antigenic lipopolysaccharide (LPS). The immunoreactivity of LPS endotoxin thought to promote susceptibility to inflammation and disease. The pathogenesis of the more common diseases of the esophagus e.g. gastroesophageal reflux disease (GERD), esophageal dysmotility (achalasia), eosinophilic esophagitis (EoE), Barrett’s esophagus (BE), and esophageal cancer, are well-established. Emerging data suggest however, that these are all characterized by an immune-mediated inflammatory cascade, propogated by a dysbiotic state. Thereby, the ability of the healthy “normative state” to protect against foreign bacteria is compromised. This dysbiosis thereby can create adverse inflammatory or immunoregulatory responses with progression of disease. In the normal healthy state, the esophageal microbiome is constituted in-part, by a multitude of gram positive bacteria, many of which produce antibacterial peptides called bacteriocins. Bacteriocins are selective and used to maintain population integrity by killing off foreign bacteria. When the “normative biome” is interrupted (e.g. antibiotics, medications, diet, environmental factors), the constitutional changes may allow a more hospitable imbalance favoring the proliferation of opportunistic pathogens. Therefore it seems rational that defining, perhaps that defining, perhaps cultivating, a protective bacterial community that could help prevent or mitigate inflammatory diseases of the esophagus. Furthermore, in conjunction with evidence demonstrating that some bacteriocins are cytotoxic or antiproliferative toward cancer cell lines, further exploration might provide a rich source of effective peptide-based drug targets. Therapeutic options targeting the microbiome, including prebiotics, probiotics, antibiotics and bacteriocins, have been studied, albeit the attributable effects on the esophagus for the most part, have been unrecognized by clinicians. This review focuses on the current knowledge of the involvement of the microbiome in esophageal diseases (most notably GERD/Barrett’s esophagus/esophageal cancer) and identifies emerging new concepts for treatment.
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Acute pancreatitis with uncommon presentation of myocardial infarction

Published on: 21st May, 2020

OCLC Number/Unique Identifier: 8616347855

Acute pancreatitis is inflammation of the pancreas that may be accompanied by a systemic inflammatory response which results in impairment of the functioning of various organs, systems. Pancreatitis associated vascular complications very often cause morbidity and mortality. There are various cardiovascular complications like shock, hypovolemia, pericardial effusion, and sometimes ST–T changes in the electrocardiogram (ECG) presenting as acute myocardial infarction (AMI). Acute myocardial infarction complicating acute pancreatitis has rarely been studied and the exact process of myocardial injury still remains unclear. We here report a case of Acute Pancreatitis associated with acute myocardial Infarction.
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Autoimmune hemolytic anemia in COVID-19 patients, the « transmissible » direct Coombs test

Published on: 7th April, 2021

OCLC Number/Unique Identifier: 8999916981

Background: Like other viruses, the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) appears to be responsible for several autoimmune complications. The occurrence of autoimmune hemolytic anemia has been described in several case reports. This AIHA was also noticeable by the important number of blood transfusions required for COVID-19 (coronavirus disease 2019) patients. By investigating RBC coating autoantibodies, this article attempts to clarify the autoimmune aspect of the anemia in the context of SARS-CoV-2 infection. Results: A large population of COVID-19 patients selected at Saint-Luc University Hospital showed an average of 44% DAT positivity. In this population, the intensive care patients were more prone to DAT positivity than the general ward patients (statistically significant result). The positive DAT appeared « transmissible » to other RBCs via COVID-19 DAT-positive patient’s plasma. Conclusion: The strongest hypothesis explaining this observation is the targeting of cryptic antigens by autoantibodies in COVID-19 patients.
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Demographic profile & correlation between retinal exudates and hematological parameters in leukemic patients

Published on: 4th June, 2021

OCLC Number/Unique Identifier: 9124548296

Background: Leukemia is frequently associated with fundoscopic abnormalities. However, no organized effort has been made for analyzing leukemic retinopathy in our country. This study was done to observe the demographic profile and correlation between fundoscopic findings of retinal exudates and hematological parameters in leukemic patients. Materials and Methods: The study was a hospital-based descriptive cross-sectional study among 50 leukemic patients in Medicine and Oncology departments of Bangladesh Medical College and Hospital (BMCH) from May, 2020 to October, 2020. Fundoscopic examination was done which was reviewed by an ophthalmologist. Collected data was analyzed statistically by using SPSS-17 (Chicago, Illinois). Results: Among 50 leukemic patients’, the fundal lesion was detected in 32 patients (64%), retinal exudates are rare. Only 3 patients (6%) had exudates while others (29 patients, 58%) have retinal hemorrhages. Exudates did not show any statistically significant relationship with types of leukemia (p value = 0.53). There was no statistically significant association between fundal exudates and high white cell count (p = 0.56) or low hemoglobin level (p = 0.11) or low platelet level (p = 0.11). Conclusion: This study has identified retinopathy occurring frequently in leukemic patients. Therefore, an adequate attention should be paid at fundoscopic evaluation while treating leukemic patients. 
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Biomarkers in Enteropathic Arthritis

Published on: 4th June, 2020

OCLC Number/Unique Identifier: 8616347490

Inflammatory Bowel Disease (IBD)-associated arthritis is called Enteropathic Arthritis (EA) which is classified among the group of Spondyloarthritis (SpA), because its presentation is variable. The current trend is to classify them as autoinflammatory rather than autoimmune diseases, since no antibodies have yet been identified. The study of biomarkers (BM) will help us with early identification and hence, to provide treatment in the early stages, prior to radiographic progression, which will enable prompt identification of the disease phenotype. 42 patients diagnosed with IBD were included, of which 48% were females; the mean age of the study group was 48.12 ± 5.02 (95% CI). The average time of evolution of disease was 37.57 ± 14.28 months; most patients referred to the rheumatologist had a diagnosis of ulcerative colitis (83%). According to our analysis, we were able to determine that the three most significant variables influencing the development of sacroiliitis were: Lactoferrin, ANCA and HLA B27 (p < 0.5). The variable that can be ruled out because of its almost neglectable contribution was fecal calprotectin.
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Features of Interferon and Cytokine Status in Atopic Dermatitis

Published on: 29th May, 2017

OCLC Number/Unique Identifier: 7317651633

The insufficiency of interferon production and the cytokine imbalance in patients with atopic dermatitis, especially in combination with persistent herpes virus infection, has been identified. The expediency of the use of interferon inducer Cycloferon in the treatment of chronic atopic dermatitis has been shown.
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Prevalence of reported drug allergy and its impact on Beta lactam use with financial and health implications

Published on: 22nd August, 2017

OCLC Number/Unique Identifier: 7317598807

Background:While recognition and documentation of true drug allergy is critically important, most physicians acknowledge that its prevalence is likely overestimated, often on the basis of historical, sometimes anecdotal evidence. Correct or not, once applied, drug allergy labels may result in altered, potentially inferior therapy, increased costs and prolonged hospitalisation. Objective:Estimate the point prevalence, accuracy and symptomatology of self-reported drug allergy in a typical, large NHS Acute Trust adult inpatient population. In the subset with penicillin allergy (PA), estimate additional management costs from the use of alternative antibiotics and readmission rates in the previous 5 years. Methods:Data on self-reported drug allergies were extracted from 440 adult inpatient prescription charts over a 4 month period. Where penicillin allergy (PA) was reported, alternative antibiotic regimens were recorded and their additional costs calculated. Hospital electronic records were used to assess readmission rates of PA patients. Results:194/440 inpatients (44.5%) reported at least one drug allergy. Antibiotic allergy was most commonly reported (51%), followed by analgesic (23%) and antiemetic (12%) allergy. PA accounted for 76% of reported antibiotic allergy. The commonest reported symptoms were cutaneous (42%) and gastrointestinal (18%). Where antibiotic therapy was required for patients with PA to manage acute infections, Ciprofloxacin, Clarithromycin, Teicoplanin, Clindamycin and Cefuroxime were the most commonly employed alternatives. Extrapolation of these figures to include the entire Trust inpatient population suggested that the use of alternative antibiotics in PA patients incurred additional annual expenditure of £268,000. Further, 87% of PA patients had been admitted more than once in the preceding 5 years, with 74% requiring further courses of antibiotics during these admissions. Conclusion:Self-reported drug allergy, and in particular PA, is common in hospital inpatient populations and, in addition to the potentially unnecessary hazards to individual patients resulting from the use of alternative antibiotics, results in a considerable additional financial burden to the healthcare system. This problem could be eliminated by the provision of a nationwide and equitable tertiary Allergy service.
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Nursing Care of ICU Patients Lightly Sedated with Dexmedetomidine

Published on: 22nd December, 2016

OCLC Number/Unique Identifier: 1026798761

Background: Intensive care patients are often in need of sedation to endure being intubated. Light sedation is increasingly common since it has been proved to offer benefits such as faster recovery to patients. Aim: The aim of this study was to describe critical care nurses’ experiences of nursing patients lightly sedated with dexmedetomidine. Research Methodology: Qualitative personal interviews were conducted during 2015 with 10 critical care nurses in Sweden. Interview transcripts were analysed using inductive qualitative thematic analysis. Results: Light sedation of the patient facilitated communication and interaction with him or her, and the relationship between the patient and his or her family members. Dexmedetomidine was described as a fairly new drug, and the critical care nurses stated that they needed more knowledge about it and about sedation scales in order to learn more about the drug’s mechanism of action and its potential side effects on patients. Conclusion: It is important to critical care nurses to learn more about dexmedetomidine and about sedation scales to assess levels of sedation, as light sedation has been shown to benefit the patient as opposed to deep sedation that can increase recovery time.
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