Andrzej K. Jaworek

Protective Effect of Melatonin on Acute Pancreatitis

Melatonin, a product of the pineal gland, is released from the gut mucosa in response to food ingestion. Specific receptors for melatonin have been detected in many gastrointestinal tissues including the pancreas. Melatonin as well as its precursor, L-tryptophan, attenuates the severity of acute pancreatitis and protects the pancreatic tissue from the damage caused by acute inflammation. The beneficial effect of melatonin on acute pancreatitis, which has been reported in many experimental studies and supported by clinical observations, is related to: (1) enhancement of antioxidant defense of the pancreatic tissue, through direct scavenging of toxic radical oxygen (ROS) and nitrogen (RNS) species, (2) preservation of the activity of antioxidant enzymes; such as superoxide dismutase (SOD), catalase (CAT), or glutathione peroxidase (GPx), (3) the decline of pro-inflammatory cytokine tumor necrosis α (TNFα) production, accompanied by stimulation of an anti-inflammatory IL-10, (4) improvement of pancreatic blood flow and decrease of neutrophil infiltration, (5) reduction of apoptosis and necrosis in the inflamed pancreatic tissue, (6) increased production of chaperon protein (HSP60), and (7) promotion of regenerative process in the pancreas. Conclusion. Endogenous melatonin produced from L-tryptophan could be one of the native mechanisms protecting the pancreas from acute damage and accelerating regeneration of this gland. The beneficial effects of melatonin shown in experimental studies suggest that melatonin ought to be employed in the clinical trials as a supportive therapy in acute pancreatitis and could be used in people at high risk for acute pancreatitis to prevent the development of pancreatic inflammation.

Pinealectomy aggravates acute pancreatitis in the rat.

Melatonin, a pineal indoleamine, protects the pancreas against acute damage; however, the involvement of the pineal gland in the pancreatoprotective action of melatonin is unknown. The primary aim of this study was to determine the effects of pinealectomy on the course of acute caerulein-induced pancreatitis (AP) in rats. AP was induced by a subcutaneous infusion of caerulein (25 μg/kg) into pinealectomized or sham-operated animals. Melatonin (5 or 25 mg/kg) was given via intraperitoneal (ip) injection 30 min prior to the induction of AP. The pancreatic content of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal (MDA + 4HNE) and the activity of an antioxidative enzyme, glutathione peroxidase (GSH-Px), were measured in each group of rats. Melatonin blood levels were measured by radioimmunoassay (RIA). In the sham-operated rats, AP was confirmed with histological examination and manifested as pancreatic edema and an increase in the blood lipase level (by 1,500%). In addition, the pancreatic content of MDA+ 4HNE was increased by 200%, and pancreatic glutathione peroxydase (GSH-Px) activity was reduced by 40%. Pinealectomy significantly aggravated the histological manifestations of AP, reduced the GSH-Px activity and markedly augmented the levels of MDA+ 4HNE in the pancreas of rats with or without AP as compared to sham-operated animals. Melatonin was undetectable in the blood of the pinealectomized rats with or without AP. Treatment with melatonin (25 mg/kg, ip) prevented the development of AP in the sham-operated rats and significantly reduced pancreatic inflammation in the animals previously subjected to pinealectomy. In conclusion, pineal melatonin contributes to the pancreatic protection through the activation of the antioxidative defense mechanism in pancreatic tissue as well as its direct antioxidant effects.

Elevated cerebrospinal fluid interleukin-17A and interferon-γ levels in early asymptomatic neurosyphilis.

Background The mechanisms underlying the process of Treponema pallidum clearance from the central nervous system have not yet been established. Considering that neurosyphilis is associated with mild cerebrospinal fluid (CSF) pleocytosis with a lymphocytic predominance, it has been suggested that cells involved in the adaptive immune response may play a role in this process. In the current study, we assessed the cytokine production profile of T-helper cells in the serum and CSF of patients with early syphilis, with and without CSF abnormalities. Methods Cerebrospinal fluid and blood samples were collected from 33 patients with secondary and early latent syphilis. Five patients (15%) had a reactive CSF Venereal Disease Research Laboratory test without any accompanying neurological symptoms. According to the Centers of Disease Control and Prevention classification, they were diagnosed with asymptomatic neurosyphilis. Serum and CSF levels of interferon-&ggr; (IFN-&ggr;; Th1-type cytokine), interleukin-4 (IL-4; Th2-type cytokine), and interleukin-17A (IL-17A; Th17-type cytokine) were determined by enzyme-linked immunosorbent assay. Results Patients with asymptomatic neurosyphilis had significantly higher levels of IL-17A (8-fold) and IFN-&ggr; (7.8-fold) in the CSF compared with patients in the no-neurosyphilis group. Six individuals had CSF pleocytosis but a negative CSF Venereal Disease Research Laboratory test result (presumptive neurosyphilis group). In this group, CSF IFN-&ggr; and CSF IL-17A levels were also significantly elevated when compared with no-neurosyphilis group. There was no correlation between serum and CSF concentrations of IL-17A. However, CSF pleocytosis correlated positively with both CSF IL-17A (r = 0.4, P = 0.01) and IFN-&ggr; (r = 0.42, P = 0.01). Conclusions Increased CSF levels of IFN-&ggr; and IL-17A in syphilitic patients with CSF abnormalities suggest that cells of adaptive immunity (probably T-helper cells producing IFN-&ggr; and IL-17) may contribute to the inflammatory response associated with neurosyphilis. In addition, the lack of correlation between serum and CSF IL-17A levels suggests intrathecal production of this cytokine. Further studies are needed to establish the exact nature of the immune response accompanying neurosyphilis and its clinical significance.

Association of CSF glucose concentration with neurosyphilis diagnosis

The most specific criterion for diagnosing neurosyphilis is a reactive CSF VDRL. Unfortunately, there are in Europe, including Poland small number of specialized laboratories for serological diagnosis of syphilis. Thus, CSF serology results are obtained with delay. Therefore, the decision on recommended therapy for neurosyphilis is taken on the basis of CSF basic tests. In this paper we attempt to determine the utility of CSF glucose concentration and its cut-off values in prediction of asymptomatic neurosyphilis. CSF and blood were collected from 55 HIV-uninfected patients with syphilis of unknown duration. Patients with neurosyphilis (14.5%) were characterized by higher CSF pleocytosis (p<0.0001), elevated CSF protein concentration (p<0.05) and lower CSF glucose concentration (p<0.0001). Multivariate regression analysis identified CSF pleocytosis and CSF glucose concentration as the two independent predictors of reactive CSF VDRL (p<0.0001). In the selected group of patients with CSF pleocytosis ≥5/µL (n=25) CSF glucose concentration ≤2.72 mmol/L was associated with 100% sensitivity (95%CI: 63–100%) and 100% specificity (95%CI: 75.3–100%) for reactive CSF VDRL. CSF glucose concentration may be particularly useful as a predictive marker of neurosyphilis in HIV uninfected patients with syphilis of unknown duration with CSF plecytosis ≥5/µL.

Drug-induced linear IgA bullous dermatosis after discontinuation of cefuroxime axetil treatment

BACKGROUND Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare autoimmune blistering disorder. The disease may be either idiopathic or druginduced. Over the past 30 years, approximately one hundred LABD cases have been described as induced by a wide range of drugs, chiefly antibiotics. MAIN OBSERVATIONS We report the case of 37-year-old woman who developed pruritic bullous lesions spread all over the body three weeks after her last dose of cefuroxime axetil. Antibiotic therapy was started due to rhino-sinusitis. CONCLUSIONS In most reported cases of drug-induced LABD, skin lesions occur within the time of drug administration. However, the onset of disease may be even after discontinuation of treatment. It seems that in such cases, other clinical conditions (like infection) act, as cofactors of immunologic response.

The Role of Melatonin in Pancreatic Protection: Could Melatonin be Used in the Treatment of Acute Pancreatitis?

Acute pancreatitis is a disease, which could be manifested as either a mild edematous form or a more severe necrotizing pancreatitis which has a poor prognosis. The etiology and pathogenesis of this ailment is not completely clear. Melatonin is an indoleamine which is produced from L-tryptophan in the pineal gland and in the other tissue including gastrointestinal tract. Both melatonin and its precursor have been demonstrated to protect the pancreas against acute pancreatitis and to attenuate pancreatic tissue damage. In the pancreas melatonin and L-tryptophan activate complex mechanisms which involve direct scavenging of the radical oxygen and nitrogen species, activation of antioxidant enzymes (catalase, superoxide dysmutase, glutation peroxidase), reduction of pro-inflammatory cytokines and prostaglandins, activation of heat shock protein, and a decrease of necrosis and increase of regeneration in the pancreas. There are several arguments for the idea that endogenous melatonin produced in the pineal gland and in the gastrointestinal system could be the part of a native mechanisms for protecting the pancreas against acute damage: 1/ the melatonin precursor L-tryptophan exerts similar protective effect as melatonin, 2/ application of the melatonin receptor antagonist, luzindole aggravates acute pancreatitis, 3/ pinealectomy results in the exacerbation of acute pancreatitis, 4/ low melatonin plasma levels are associated with an increased risk of severe acute pancreatitis. These observations leads to the idea that perhaps melatonin could be used in clinical trials as supportive therapy in acute pancreatitis.

Pityriasis lichenoides-like secondary syphilis and neurosyphilis in a HIV-infected patient.

Papulo- and vesiculo-necrotic lesions are rare manifestations of secondary syphilis. Until now it has been described only in HIV-infected patients with advanced stages of immunosuppression. This case report describes an unusual case of PLEVA-like syphilis in a 33-year-old man with newly diagnosed HIV infection. Despite that the CD4 cells level and viral load did not indicate the advance stage of immunosuppression, the unusual manifestation of syphilis and neurosyphilis occurred. The presented case indicates the need for HIV screening in every patient with syphilis especially when the clinical manifestation is unusual. Importance of syphilis testing in every case with atypical rashes should be also highlighted.

Utility of post-treatment follow-up visit at 3 months in patients treated for early syphilis

The main aim of serological post-treatment follow-up in patients treated for early syphilis is to identify treatment failure or re-infection.1 Most experts define treatment failure or re-infection as ‘serological’ when the Venereal Disease Research Laboratory (VDRL) titre increases fourfold after treatment. In addition, poor serological response is represented as failure of the VDRL titre …

Stress coping mechanisms in patients with chronic dermatoses

Summary Objective. The results of numerous studies of today confirm that persons suffering from psychosomatic disorders are not able to effectively cope with stress. The experience of stress is also frequently combined with the occurrence or aggravation of various skin diseases. The goal of our study was to identify the predominant ways of coping with stress in the group of patients with chronic dermatoses. Methods. The group under study included patients receiving treatment in the Dermatology Clinic of Collegium Medicum, Jagiellonian University. They were either hospitalized patients or those who came for control examinations at the Outpatient Clinic. Evaluation of the forms of coping with stress was conducted with the help of the Endler and Parker Questionnaire – CISS. Results . They significantly more often apply the style of coping focused on avoiding (p-value= 0.0056). It also turned out that the patients in the dermatological groups manifested a constant tendency to get involved in vicarious activities (p-value=0.0247). Discussion. The results of the presented study indicate that there is a statistically significant difference between the patients with dermatological disorders and those in the control group as regards their ways of coping with stress. Conclusion . The results obtained in the discussed study may be a starting point for designing a complex support for the patients with skin diseases. The therapeutic technique that may prove helpful for this group of patients is the cognitive-behavioral therapy (CTB). psoriasis / stress coping mechanisms / connective tissue diseases / rosacea