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Hypothesis: Chronic fatigue syndrome is caused by dysregulation of hydrogen sulfide metabolism
... Dysregulation of H 2 S may play a role in ME/CFS since the gas can affect adenosine triphosphate (ATP) production from oxidative phosphorylation (73). H 2 S can induce a torpor-like state in mice (74). ...
... What might cause the hypometabolic state reported in ME/CFS? Dysregulated H 2 S production can induce a hypometabolic, torporlike state in mice (73,74). In addition, any of several stressors, including viral infection and oxidative stress, can trigger evolutionarily conserved protective responses that operate at the level of both the cell (the cell danger response) (148) and the whole organism (the integrated stress response, hibernation, and the state of dauer in Caenorhabditis elegans) (121,149,150). ...
... These protective responses generally are reversible when the stressor no longer is present. Since dysregulated H 2 S production can induce a hypometabolic, torpor-like state in mice Paul (74), H 2 S production may be one potential switch (73). Since protein translation consumes considerable ATP, a reduction in protein translation thereby makes ATP available for repair of injury and preservation of vital functions. ...
Although most patients recover from acute COVID-19, some experience postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC). One subgroup of PASC is a syndrome called “long COVID-19,” reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition, often triggered by viral and bacterial infections, leading to years-long debilitating symptoms including profound fatigue, postexertional malaise, unrefreshing sleep, cognitive deficits, and orthostatic intolerance. Some are skeptical that either ME/CFS or long COVID-19 involves underlying biological abnormalities. However, in this review, we summarize the evidence that people with acute COVID-19 and with ME/CFS have biological abnormalities including redox imbalance, systemic inflammation and neuroinflammation, an impaired ability to generate adenosine triphosphate, and a general hypometabolic state. These phenomena have not yet been well studied in people with long COVID-19, and each of them has been reported in other diseases as well, particularly neurological diseases. We also examine the bidirectional relationship between redox imbalance, inflammation, energy metabolic deficits, and a hypometabolic state. We speculate as to what may be causing these abnormalities. Thus, understanding the molecular underpinnings of both PASC and ME/CFS may lead to the development of novel therapeutics.
... 32 The mitochondrial electron transport/ respiratory chain is critical for maintaining effective ATP levels, 33 suggesting that a contributor to fatigue could be caused by a reduction in the capacity of mitochondria to use oxygen and synthesize ATP. 34,35 It has been hypothesized that the inability of mitochondria to produce a sufficient supply of energy in the form of ATP plays a major role in fatigue. 35 Our results support this hypothesis by demonstrating that 11 genes associated with mitochondrial integrity and functions critical to ATP production were differentially expressed during EBRT. ...
... 34,35 It has been hypothesized that the inability of mitochondria to produce a sufficient supply of energy in the form of ATP plays a major role in fatigue. 35 Our results support this hypothesis by demonstrating that 11 genes associated with mitochondrial integrity and functions critical to ATP production were differentially expressed during EBRT. Eight of these 11 differentially expressed genes are directly involved in mitochondrial apoptosis pathway and signaling (AIFM2, BCL2, BCL2L1), mitochondrial membrane polarization and potential (BCL2, BCL2L1), mitochondrial transport (BCL2, BCL2L1, IMMP2L, MIPEP), and small molecular transport (SLC25A23, SLC25A37, SLC25A4 ). ...
Aims: To explore the relationship between mitochondrial dysfunction and fatigue in prostate cancer patients following external beam radiation therapy (EBRT)
Methods: Perceived fatigue (the revised Piper Fatigue Scale) and blood samples are collected at baseline, midpoint and endpoint of treatment. Microarray gene expression analysis and RT2 Profiler PCR Array System are utilized to identify differential regulation of genes involved in mitochondrial dysfunction and fatigue at the different time points compared to gene expression in the baseline samples.
Results: Mean perceived fatigue score was 1.52 (SD=1.91) at pre-radiation (baseline) increased to 2.79 (SD=2.02) at the midpoint of radiation therapy, and decreased to 2.60 (SD=2.33) by the end of radiation therapy, indicating increased fatigue at the midpoint and end of treatment (n=10). Genes with greater than 2 fold up-regulation among patients compared to the control group include neurofilament, light polypeptide [NEFL], solute carrier family 25, member 27 [SLC25A27], and translocase of inner mitochondrial membrane [TIMM9]). Genes with greater than 2 fold down-regulation in patients compared to the control group include tafazzin [TAZ] and superoxide dismutase 2, mitochondrial [SOD2]. The relationship between higher fatigue score following EBRT and gene expression profile is being evaluated for genes related to mitochondrial dysfunction (e.g. genes that regulate mitochondrial respiratory chain), other mechanisms of fatigue and novel pathways.
Conclusions: Potential findings of gene expression associated with mitochondrial function may identify possible pathways and early biomarkers of radiation-induced fatigue. Further studies exploring and validating biomarkers of mitochondrial dysfunction causing CRF will be necessary to identify novel interventional targets.
... Metabolic defects may also be reflected in abnormalities in blood flow regulation and mitochondrial function, some of which may be linked to altered endothelial nitric oxide (NO) [21] and hydrogen sulfide (H2S) [22] metabolism. NO relaxes the smooth muscles that surround arterioles and arteries, increasing the flow of blood when required. ...
... NO relaxes the smooth muscles that surround arterioles and arteries, increasing the flow of blood when required. In ME/CFS patients, reduced NO production by endothelial cells [21] may increase the constriction of arterioles and arteries, whereas a postulated deregulation of H2S [22] may lead to an inhibition of cytochrome-c oxidase and thus a reduction in mitochondrial production of ATP. A reduced blood flow or mitochondrial ATP production in critical organs, including the skeletal muscles, brain, and brain stem, could elicit a variety of somatosensory symptoms of ME/CFS, including a diminished ability to perform physical activity [23]. ...
Fatigue is a common symptom of numerous acute and chronic diseases, including myalgic encephalomyelitis/chronic fatigue syndrome, multiple sclerosis, heart failure, cancer, and many others. In these multi-system diseases the physiological determinants of enhanced fatigue encompass a combination of metabolic, neurological, and myofibrillar adaptations. Previous research studies have focused on adaptations specific to skeletal muscle and their role in fatigue. However, most have neglected the contribution of physical inactivity in assessing disease syndromes, which, through deconditioning, likely contributes to symptomatic fatigue. In this commentary, we briefly review disease-related muscle phenotypes in the context of whether they relate to the primary disease or whether they develop secondary to reduced physical activity. Knowledge of the etiology of the skeletal muscle adaptations in these conditions and their contribution to fatigue symptoms is important for understanding the utility of exercise rehabilitation as an intervention to alleviate the physiological precipitants of fatigue.
... 70,71 H2S, based on its ability to inhibit mitochondrial oxygen use, may play a part in ME/CFS. 72 Potentially it could alter redox imbalance in the brain in ME/CFS. ...
Long COVID is now well accepted as an ongoing post-viral syndrome resulting from infection of a single virus, the pandemic SARS-CoV-2. It mirrors the post-viral fatigue syndrome, Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, a global debilitating illness arising mainly from sporadic geographically-specific viral outbreaks, and from community endemic infections, but also from other stressors. Core symptoms of both syndromes are post-exertional malaise (a worsening of symptoms following mental or physical activity), pervasive fatigue, cognitive dysfunction (brain fog), and sleep disturbance. Long COVID patients frequently also suffer from shortness of breath, relating to the lung involvement of the SARS-CoV-2 virus. There is no universally accepted pathophysiology, or recognized biomarkers yet for Long COVID or indeed for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clinical case definitions with very similar characteristics for each have been defined. Chronic inflammation, immune dysfunction, and disrupted energy production in the peripheral system has been confirmed in Long COVID and has been well documented in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Neuroinflammation occurs in the brain in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome as shown from a small number of positron emission tomography and magnetic resonance spectroscopy studies, and has now been demonstrated for Long COVID. Oxidative stress, an increase in reactive oxygen and reactive nitrogen species, and free radicals, has long been suggested as a potential cause for many of the symptoms seen in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, resulting from both activation of the brain’s immune system and dysregulation of mitochondrial function throughout the body. The brain as a high producer of energy may be particularly susceptible to oxidative stress. It has been shown in peripheral immune cells that the balanced production of proteins involved in regulation of the reactive oxygen species in mitochondria is disturbed in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fluctuations in the chronic low level neuroinflammation during the ongoing course of Long COVID as well as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome have been proposed to cause the characteristic severe relapses in patients. This review explores oxidative stress as a likely significant contributor to the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and the mechanisms by which oxidative stress could cause the symptoms seen in both syndromes. Treatments that could mitigate oxidative stress and thereby lessen the debilitating symptoms to improve the life of patients are discussed.
... Метаболизм железа Гиперферритинемия [46]. Повышение уровня Снижение трансферрина, и гема биливердина, снижение -билирубина [47] повышение гема в крови [48,49] Уровень гомоцистеина Повышение в крови [50] Повышение в ЦСЖ [51] Изменение Отрицательная корреляция между снижением Снижение [53] уровня СОД СОД-3 при COVID-19 и тяжестью заболевания [52] Нейтрофильный Повышение количества нейтрофилов Нейтропения и снижение окислительного стресса, ответ и отношения нейтрофилов к лимфоцитам вторичные по отношению к изначально агрессивному с положительной корреляцией со смертностью [54] нейтрофильному ответу, истощение нейтрофилов и лимфоцитов [55] NО NOS 2 повышается у пациентов Высокий уровень NO [7]; с тяжелым течением болезни [56] уровень цитруллина повышен [57] H 2 S Повышение содержания H 2 S в крови и высокие Дисрегуляция H 2 S [59] показатели циркулирующих лимфоцитов, стимуляция H 2 S пролиферации Т-лимфоцитов [58] Метаболиты ...
The review examines the epidemiology and clinical manifestations of COVID-19 long-term neurological effects, main pathobiochemical mechanisms, and integrated circuits of redox status impairment in COVID-19, such as the decrease of adenosine triphosphate production, fatty acids levels, acylcarnitine, and amino acids, impairment of oxidative phosphorylation and glycolysis, hypometabolic state, redox imbalance with the increase of peroxides and superoxides, isoprostanes, the decrease of α-tocopherol, substances reacting with thiobarbituric acid, increased nitrosative stress with the increase of inducible synthase of nitric oxide, nitric oxide, peroxynitrite, and nitrate. Neuroprotective approaches aimed at suppressing excitotoxicity, oxidative stress, and neuroinflammation are presented. Recent data on the relationship between mechanisms of chondroitin sulfate and its derivatives (chondroitin sulfate glycoprotein disaccharide) neuroprotective effects and characteristics of their chemical structure are analyzed. The mechanism of action and neuroprotective effects of chondroitin sulfate and its derivatives in fatigue syndrome in patients with SARS-CoV2 infection are discussed (regulation of the PKC/PI3K/Akt activity, the increase of heme oxygenase-1 level, the decrease of reactive oxygen species). The position that chondroitin sulfate and its derivatives can become promising drugs to prevent the long-term neurological effects of COVID-19 is reasoned.
... Cystathionine gamma lyase, 3-Effect of a Hydrogen Sulfide Donor on Skeletal Muscle mercaptopyruvate sulfurtransferase and cysteine aminotransferase (CAT) can produce H 2 S in different tissues (6) . H 2 S has been found to be involved in protecting the heart against acute myocardial infarction (7) and ischemia/reperfusion injury, regulating blood pressure (8) , mediating smooth-muscle relaxation (9) and inhibiting insulin release and renin activity (10,11) In skeletal muscles, the role of H 2 S in contraction has not been fully investigated although it was hypothesized that impaired formation may be involved in chronic fatigue syndrome (2,12,13) , Therefore, this work was designed to study the effect of an H 2 S donor; sodium hydrosulfide (NaHS) on skeletal muscle contraction and fatigue in adult male albino rat' gastrocnemius muscle and the possible interaction with nitric oxide. ...
... Similarly, recent studies have confirmed that H 2 S plays an antiatherosclerotic role, and its deficiency leads to early development and progression of atherosclerosis (Wang et al. 2009). In agreement with this view, it was hypothesized that dysregulation of H 2 S metabolism is involved in chronic fatigue syndrome, also called myalgic encephalomyelitis (Lemle 2009). Among the known cellular targets of H 2 S, potassium channels have been the first to be discovered (Tang et al. 2005;Zhao et al. 2001). ...
Elevated homocysteine (Hcy), i.e., hyperhomocysteinemia (HHcy) causes skeletal muscle myopathy. Among many cellular and metabolic alterations caused by HHcy, oxidative and endoplasmic reticulum (ER)-stress are considered the major ones; however, the precise molecular mechanism(s) in this process is unclear. Nevertheless, there is no treatment option available to treat HHcy-mediated muscle injury. Hydrogen sulfide (H2S) is increasingly recognized as a potent anti-oxidant, anti-apoptotic/necrotic/pyroptotic, and anti-inflammatory compound and also has been shown to improve angiogenesis during ischemic injury. Patients with CBS mutation produce less H2S, making them vulnerable to Hcy-mediated cellular damage. Many studies reported bidirectional regulation of ER-stress in apoptosis through JNK activation, and concomitant attenuation of cell proliferation and protein synthesis via PI3K/AKT axis. Whether H2S mitigates these detrimental effects of HHcy on muscle remains unexplored. In this review, we discuss molecular mechanisms of HHcy-mediated oxidative/ER-stress responses, apoptosis, angiogenesis, and atrophic changes in skeletal muscle and how H2S can restore skeletal muscle homeostasis during HHcy condition. This review also highlights the molecular mechanisms on how H2S could be developed as a clinically relevant therapeutic option for chronic conditions that are aggravated by HHcy.
... Similarly, recent studies have confirmed that H 2 S plays an anti-atherosclerotic role, and its deficiency leads to early development and progression of atherosclerosis (Wang et al. 2009). In agreement with this view, it was hypothesized that dysregulation of H 2 S metabolism is involved in chronic fatigue syndrome, also called myalgic encephalomyelitis (Lemle 2009). Among the known cellular targets of H 2 S, potassium channels have been the first to be discovered (Tang et al. 2005;Zhao et al. 2001). ...
Elevated homocysteine (Hcy), i.e., hyperhomocysteinemia (HHcy), causes skeletal muscle myopathy. Among many cellular and metabolic alterations caused by HHcy, oxidative and endoplasmic reticulum (ER) stress are considered the major ones; however, the precise molecular mechanism(s) in this process is unclear. Nevertheless, there is no treatment option available to treat HHcy-mediated muscle injury. Hydrogen sulfide (H2S) is increasingly recognized as a potent anti-oxidant, anti-apoptotic/necrotic/pyroptotic, and anti-inflammatory compound and also has been shown to improve angiogenesis during ischemic injury. Patients with CBS mutation produce less H2S, making them vulnerable to Hcy-mediated cellular damage. Many studies have reported bidirectional regulation of ER stress in apoptosis through JNK activation and concomitant attenuation of cell proliferation and protein synthesis via PI3K/AKT axis. Whether H2S mitigates these detrimental effects of HHcy on muscle remains unexplored. In this review, we discuss molecular mechanisms of HHcy-mediated oxidative/ER stress responses, apoptosis, angiogenesis, and atrophic changes in skeletal muscle and how H2S can restore skeletal muscle homeostasis during HHcy condition. This review also highlights the molecular mechanisms on how H2S could be developed as a clinically relevant therapeutic option for chronic conditions that are aggravated by HHcy.
COVID-19 has become the first modern-day pandemic of historic proportion, affecting >600 million individuals worldwide and causing >6.5 million deaths. While acute infection has had devastating consequences, postacute sequelae of SARS-CoV-2 infection appears to be a pandemic of its own, impacting up to one-third of survivors and often causing symptoms suggestive of cardiovascular phenomena. This review will highlight the suspected pathophysiology of postacute sequelae of SARS-CoV-2, its influence on the cardiovascular system, and potential treatment strategies.
Despite the genetic basis of malignant hyperthermia (MH) syndrome are well established, the diagnosis still needs an invasive procedure called In Vitro Contracture Test (IVCT). This strongly suggests that alternative/additive mechanisms are involved in the MH syndrome susceptibility. Recently, hydrogen sulfide (H2S) signaling has been evaluated as a new player in MH syndrome. Indeed, in MHS subjects there are local augmented levels of CBS-derived H2S within the skeletal muscle, not valuable in plasma. Being H2S molecular targets, Kv7 and KATP channels are involved in anomalous behavior observed in SKM of susceptible patients. Persulfidation has been demonstrated as the molecular mechanism through which H2S modifies Kv7 channels activity switching the hyperpolarizing response (resting condition) to depolarizing (contraction). Finally, the discovery of H2S signaling and potassium channel involvement in the MH appearance could help to better clarify the molecular basis of the syndrome and to define a new less invasive procedure for diagnosis.
The presence of H2S pathway in skeletal muscle (SKM) has been recently established. SKM expresses the three constitutive H2S generating enzymes in animals and humans and it actively produces H2S. The main recognized molecular targets of H2S, i.e. potassium channels and phosphodiesterases, have been evaluated in SKM physiology in order to hypothesize a role for H2S signaling. SKM dysfunctions, including muscular dystrophy and malignant hyperthermia, have been also evaluated as conditions in which H2S‐pathway and the trans‐sulfuration pathway have been suggested to be involved. The intrinsic complexity of the molecular mechanisms involved in E‐C coupling together with the scarcity of SKM‐related disorders pre‐clinical models has impaired the advance in knowledge on the skeletal muscle function. Here we have addressed the role of H2S pathway in the E‐C coupling and the relative importance of cystathionine β‐synthase (CBS), cistathionine γ‐lyase (CSE) and 3‐mercaptopyruvate sulfurtransferase (3‐MST) in SKM diseases.
Background:
Cancer-related fatigue (CRF) is associated with negative health outcomes and decreased health-related quality of life; however, few longitudinal studies have investigated molecular-genetic mechanisms of CRF.
Objective:
The objective of this study was to describe relationships between mitochondria-related gene expression changes and self-reported fatigue in prostate cancer patients receiving external beam radiation therapy (EBRT).
Methods:
A prospective, exploratory, and repeated-measures design was used. Self-report questionnaires and peripheral whole-blood samples were collected from 15 patients at 7 time points. Baseline data were compared against 15 healthy controls. The Human Mitochondria RT Profiler PCR Array was used to identify differential regulation of genes involved in mitochondrial biogenesis and function.
Results:
Compared with baseline, there were significant increases in fatigue scores (P = .02-.04) and changes in mitochondria-related gene expression (P = .001-.05) over time. Mean fatigue scores were 1.66 (SD, 1.66) at baseline, 3.06 (SD, 1.95) at EBRT midpoint, 2.98 (SD, 2.20) at EBRT completion, and 2.64 (SD, 2.56) at 30 days after EBRT. Over time, 11 genes related to mitochondrial function and structure were differentially expressed. Of these 11 genes, 3 (BCL2L1, FIS1, SLC25A37) were more than 2.5 fold up-regulated, and 8 (AIFM2, BCL2, IMMP2L, MIPEP, MSTO1, NEFL, SLC25A23, SLC25A4) were greater than 2-fold down-regulated. Furthermore, 8 genes (AIFM2, BCL2, FIS1, IMMP2L, MSTO1, SLC25A23, SLC25A37, SLC25A4) were significantly associated with the changes in fatigue scores.
Conclusion:
This study provides preliminary evidence that 8 mitochondrial function genes were significantly associated with fatigue in prostate cancer patients during EBRT.
Implications for practice:
These findings identify possible pathways and early biomarkers for targeting novel interventions for CRF.
Hydrogen sulfide (H(2)S) is produced by indigenous sulfate-reducing bacteria in the large intestine and represents an environmental insult to the colonic epithelium. Clinical studies have linked the presence of either sulfate-reducing bacteria or H(2)S in the colon with chronic disorders such as ulcerative colitis and colorectal cancer, although at this point, the evidence is circumstantial and underlying mechanisms remain undefined. We showed previously that sulfide at concentrations similar to those found in the human colon induced genomic DNA damage in mammalian cells. The present study addressed the nature of the DNA damage by determining if sulfide is directly genotoxic or if genotoxicity requires cellular metabolism. We also questioned if sulfide genotoxicity is mediated by free radicals and if DNA base oxidation is involved. Naked nuclei from untreated Chinese hamster ovary cells were treated with sulfide; DNA damage was induced by concentrations as low as 1 micromol/L. This damage was effectively quenched by cotreatment with butylhydroxyanisole. Furthermore, sulfide treatment increased the number of oxidized bases recognized by formamidopyrimidine [fapy]-DNA glycosylase. These results confirm the genotoxicity of sulfide and strongly implicate that this genotoxicity is mediated by free radicals. These observations highlight the possible role of sulfide as an environmental insult that, given a predisposing genetic background, may lead to genomic instability or the cumulative mutations characteristic of colorectal cancer.
In order to investigate the effect of n-hexane and its metabolites on the Central Nervous System (CNS), we treated mice with n-hexane and 2,5-hexanedione (2,5-HD) by intraperitoneal (i.p.) administration. Gascromatographic mass spectrometric (GCMS) analyses of striatum and cerebellum revealed a consistent increase of 2,5-HD concentration at 0.5 and 2 hours after treatment and a decline to baseline levels at 24 hours. Traces of 2,5-HD were detected in the brain of control animals. Biochemical analyses revealed a precocious, short lasting, significant increase of striatal dopamine (DA) and homovanillic acid (HVA) levels. A significant increase of striatal synaptosomal DA uptake, suggesting a DA releasing effect on the dopaminergic terminals, was also observed. These results support the hypothesis of a possible role of n-hexane and its metabolites in inducing parkinsonism in humans and animals.
A number of scavengers of reactive oxygen species (ROS) were found to be protective against cell death induced by hydrogen sulfide (H2S) in isolated hepatocytes. The H2O2 scavengers alpha-ketoglutarate and pyruvate, which also act as energy substrate metabolites, were more protective against H2S toxicity than lactate which is only an energy substrate metabolite. All of these results suggest that H2S toxicity is dependent on ROS production. We measured ROS formation directly in hepatocytes using the fluorogenic dichlorofluorescin method. H2S-induced ROS formation was dose dependent and pyruvate inhibited this ROS production. Non-toxic concentrations of H2S enhanced the cytotoxicity of H2O2 generated by glucose/glucose oxidase, which was inhibited by CYP450 inibitors. Furthermore, hepatocyte ROS formation induced by H2S was decreased by CYP450 inhibitors cimetidine and benzylimidazole. These results suggest that CYP450-dependant metabolism of H2S is responsible for inducing ROS production. H2S-induced cytotoxicity was preceded by mitochondrial depolarization as measured by rhodamine 123 fluorescence. Mitochondrial depolarization induced by H2S was prevented by zinc, methionine and pyruvate all of which decreased H2S-induced cell death. Treatment of H2S poisoning may benefit from interventions aimed at minimizing ROS-induced damage and reducing mitochondrial damage.
Mammals normally maintain their core body temperature (CBT) despite changes in environmental temperature. Exceptions to this
norm include suspended animation–like states such as hibernation, torpor, and estivation. These states are all characterized
by marked decreases in metabolic rate, followed by a loss of homeothermic control in which the animal's CBT approaches that
of the environment. We report that hydrogen sulfide can induce a suspended animation-like state in a nonhibernating species,
the house mouse (Mus musculus). This state is readily reversible and does not appear to harm the animal. This suggests the possibility of inducing suspended
animation-like states for medical applications.
There is now evidence that chronic fatigue syndrome (CFS) is accompanied by immune disorders and by increased oxidative stress. The present study has been designed in order to examine the serum concentrations of IgA and IgM to LPS of gram-negative enterobacteria, i.e. Hafnia alvei; Pseudomonas aeruginosa, Morganella morganii, Proteus mirabilis, Pseudomonas putida, Citrobacter koseri, and Klebsiella pneumoniae in CFS patients, patients with partial CFS and normal controls. We found that the prevalences and median values for serum IgA against the LPS of enterobacteria are significantly greater in patients with CFS than in normal volunteers and patients with partial CFS. Serum IgA levels were significantly correlated to the severity of illness, as measured by the FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory. The results show that enterobacteria are involved in the etiology of CFS and that an increased gut-intestinal permeability has caused an immune response to the LPS of gram-negative enterobacteria. It is suggested that all patients with CFS should be checked by means of the IgA panel used in the present study and accordingly should be treated for increased gut permeability.
To investigate the mechanisms and biomarker of the neuropathy induced by 2,5-hexanedione (HD), male Wistar rats were administrated HD at dosage of 200 or 400mg/kg for 8 weeks (five-times per week). All rats were sacrificed after 8 weeks of treatment and the cerebrum cortex (CC), spinal cord (SC) and sciatic nerves (SN) were dissected, homogenized and used for the determination of cytoskeletal proteins by western blotting. The levels of neurofilaments (NFs) subunits (NF-L, NF-M and NF-H) in nerve tissues of 200 and 400mg/kg HD rats significantly decreased in both the supernatant and pellet fractions. Furthermore, significant negative correlations between NFs levels and gait abnormality were observed. As for microtubule (MT) and microfilament (MF) proteins, the levels of alpha-tubulin, beta-tubulin and beta-actin in the supernatant and pellet fraction of SN significantly decreased in 200 and 400mg/kg HD rats and correlated negatively with gait abnormality. However, the contents of MT and MF proteins in CC and SC were inconsistently affected and had no significant correlation with gait abnormality. The levels of NF-L and NF-H in serum significantly increased, while NF-M, alpha-tubulin, beta-tubulin and beta-actin contents remain unchanged. A significant positive correlation (R=0.9427, P<0.01) was observed between gait abnormality and NF-H level in serum as the intoxication went on. These findings suggested that HD intoxication resulted in a progressive decline of cytoskeletal protein contents, which might be relevant to the mechanisms of HD-induced neuropathy. NF-H was the most sensitive index, which may serve as a good indicator for neurotoxicity of n-hexane or HD.
Infectious Diseases Society of America Diagnosis and treatment of diabetic foot infections
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Lipsky BA, Berendt AR, Deery HG, Embil JM, Joseph WS, Karchmer AW, et al. Infectious Diseases Society of America. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2004;39(7):885–910. Epub 2004 Sep 10. Mesut Mutluoglu Department of Underwater and Hyperbaric Medicine, Gulhane Military Medical Academy Haydarpasa Teaching Hospital, 34668 Uskudar, Istanbul,