Arachidonic Acid Pathways and Male Fertility: A Systematic Review.

Arachidonic acid (AA) is a polyunsaturated fatty acid that is involved in male fertility. Human seminal fluid contains different prostaglandins: PGE (PGE1 and PGE2), PGF2α, and their specific 19-hydroxy derivatives, 18,19-dehydro derivatives of PGE1 and PGE2. The objective of this study is to synthesize the available literature of in vivo animal studies and human clinical trials on the association between the AA pathway and male fertility. PGE is significantly decreased in the semen of infertile men, suggesting the potential for exploitation of PGE agonists to improve male fertility. Indeed, ibuprofen can affect male fertility by promoting alterations in sperm function and standard semen parameters. The results showed that targeting the AA pathways could be an attractive strategy for the treatment of male fertility.

The Importance of Nutraceuticals in COVID-19: What's the Role of Resveratrol?

Since COVID-19 has affected global public health, there has been an urgency to find a solution to limit both the number of infections, and the aggressiveness of the disease once infected. The main characteristic of this infection is represented by a strong alteration of the immune system which, day by day, increases the risk of mortality, and can lead to a multiorgan dysfunction. Because nutritional profile can influence patient's immunity, we focus our interest on resveratrol, a polyphenolic compound known for its immunomodulating and anti-inflammatory properties. We reviewed all the information concerning the different roles of resveratrol in COVID-19 pathophysiology using PubMed and Scopus as the main databases. Interestingly, we find out that resveratrol may exert its role through different mechanisms. In fact, it has antiviral activity inhibiting virus entrance in cells and viral replication. Resveratrol also improves autophagy and decreases pro-inflammatory agents expression acting as an anti-inflammatory agent. It regulates immune cell response and pro-inflammatory cytokines and prevents the onset of thrombotic events that usually occur in COVID-19 patients. Since resveratrol acts through different mechanisms, the effect could be enhanced, making a totally natural agent particularly effective as an adjuvant in anti COVID-19 therapy.

CYP-derived eicosanoids: Implications for rheumatoid arthritis.

Today the role of cytochrome P450 metabolites in inflammatory rheumatic disease, such as rheumatoid arthritis (RA) is still poorly understood. In this review we survey the current knowledge on cytochrome P450 metabolites in rheumatoid arthritis. The balance between CYP epoxygenase- and CYP ω- hydroxylase is correlated to the regulation of NF-κB. In RA patients synovial fluid there are higher levels of IL-6, which suppresses activities of CYP enzymes, such as CYP3A, CYP2C19, CYP2C9, and CYP1A2. EETs have anti-inflammatory effects, probably attributed to the PPARγ activation. EETs inhibit bone resorption and osteoclastogenesis, and can be considered as an innovative therapeutic strategy for rheumatoid arthritis. In reference to the CYP É·-hydroxylase pathway, 20-HETE is a pro-inflammatory mediator. While there is scarce information on the role of 20-HETE inhibitors and its antagonists in rheumatoid arthritis, the elevation of EETs levels by sEH inhibitors is a promising therapeutic strategy for rheumatoid arthritis patients. In addition, hybrid compounds, such as sEH inhibitors/FLAP inhibitors, or sEHI combined with NSAIDs/COXIBs are also important therapeutic target. However, studies investigating the effects of inflammation and rheumatic disease on CYP-mediated eicosanoid metabolism are necessary. Obtaining a better understanding of the complex role of CYP-derived eicosanoids in inflammatory rheumatic disease, such as rheumatoid arthritis will provide valuable insight for basic and clinical researchers investigation.

5,10-Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms: genotype frequency and association with homocysteine and folate levels in middle-southern Italian adults.

Two genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene (C677T and A1298C) can influence the plasma homocysteine (Hcy) levels, especially in the presence of an inadequate folate status. The aim of this study was to evaluate the frequencies of C677T and of A1298C MTHFR polymorphisms and their correlation with Hcy and serum folate concentrations in a population of blood donors living in a region of middle-southern Italy (the Molise Region). One hundred ninety seven blood donors were studied for total plasma Hcy, serum folate and C677T and A1298C MTHFR genotypes. The frequency of C677T genotypes was 20.8% (CC), 49.8% (CT) and 29.4% (TT); for the A1298C genotypes: 48.7% (AA), 43.7% (AC) and 7.6% (CC). Hcy and serum folate concentrations were significantly different among genotypes of the C677T polymorphism (CC versus CT versus TT: <0.0001 both for Hcy and folate), with Hcy values increasing, and serum folate decreasing, from CC to TT subjects. Regarding to A1298C polymorphism, the difference among genotypes (AA versus AC versus CC; p: 0.026 for Hcy and 0.014 for serum folate), showed an opposite trend for both parameters, with Hcy higher in the wild-type and lower in the homozygotes and serum folate higher in CC than in AA subjects. In conclusion, we found a high frequency of MTHFR allele associated with high level of Hcy and low levels of folate in an Italian southern population.

Health Economic Evaluations of Hemochromatosis Screening and Treatment: A Systematic Review.

BACKGROUND: Hereditary hemochromatosis (HH) is an autosomal recessive disorder that leads to iron overload and multiorgan failure. OBJECTIVES: The aim of this systematic review was to provide up-to-date evidence of all the current data on the costs and cost effectiveness of screening and treatment for HH. METHODS: We searched PubMed, Cochrane Library, National Health Service Economic Evaluation Database (NHSEED), Cost-Effectiveness Analysis Registry (CEA Registry), Health Technology Assessment Database (HTAD), Centre for Reviews and Dissemination (CRD), and Econlit until April 2023 with no date restrictions. Articles that reported cost-utility, cost-description, cost-minimization, cost-effectiveness, or cost-benefit analyses for any kind of management (drugs, screening, etc.) were included in the study. Patients with HH, their siblings, or individuals suspected of having HH were included in the study. All screening and treatment strategies were included. Two authors assessed the quality of evidence related to screening (either phenotype or genotype screening) and treatment (phlebotomy and electrophoresis). Narrative synthesis was used to analyse the similarities and differences between the respective studies. RESULTS: Thirty-nine papers were included in this study. The majority of the studies reported both the cost of phenotype screening, including transferrin saturation (TS), serum ferritin, and liver biopsy, and the cost of genotype screening (HFE screening, C282Y mutation). Few studies reported the cost for phlebotomy and erythrocytapheresis treatment. Data revealed that either phenotype or genotype screening were cost effective compared with no screening. Treatment studies concluded that erythrocytapheresis might be a cost-effective therapy compared with phlebotomy. CONCLUSIONS: Economic studies on either the screening, or treatment strategy for HH patients should be performed in more countries. We suggest that cost-effectiveness studies on the role of deferasirox in HH should be carried out as an alternative therapy to phlebotomy.

Reporting of Adverse Drug Reactions by Dentists and Dental Patients in Albania.

BACKGROUND: Procedures on reporting adverse drug reactions (ADRs) in Albania are not yet standardised with the European Union despite continuous legislative changes. The aim of this study was to assess for the first time in Albania the reporting of ADRs by dentists and dental patients and to evaluate the frequency and timing of ADRs. METHODS: We conducted a questionnaire-based survey for dentists and dental patients in Albania on their knowledge on ADR signalling. Dentists and their patients were randomly reached in private dental clinics. Ninety-five dentists and 640 dental patients from 5 different cities in Albania agreed to participate in the study. Only dentists who were actively working on their dental clinics and who volunteered to participate in the study were considered eligible. RESULTS: The response rates were 95.0% and 91.4% for dentists and dental patients, respectively. In addition, 7.36% of dentists reported to have been informed on the national ADR signalling through conferences, but when asked about the procedures only 28.6% of them reported to have knowledge on the concrete process. None of the dental patients knew how to report ADRs. CONCLUSIONS: The findings demonstrate the complete lack of information on ADR signalling in a randomly selected group of 640 dental patients and 95 dentists surveyed. The results of the study are concerning and show that knowledge on ADR signalling should massively increase through public and social media.

Pharmacoeconomic Evaluation of Costs of Myelomeningocele and Meningocele Treatment and Screening.

Background: The prevention of myelomeningocele (MMC) and meningocele (MC) is a public health concern. A systematic review on economic factors associated with MMC and MC can help the policy makers to evaluate the cost-effectiveness of screening and treatment. To our knowledge, this is the first systematic review to provide up-to date pharmacoeconomic evidence of all economic studies present in literature on different aspects of MMC and MC. Methods: We searched in the National Health Service Economic Evaluation Database (NHSEED), PubMed, Cost-effectiveness Analysis Registry (CEA Registry), Centre for Reviews and Dissemination (CRD), Health Technology Assessment Database (HTAD), Cochrane Library, and Econlit. The PRISMA guidelines were followed in the search and evaluation of literature. Only articles in English not limited by the year of publication that fulfilled the eligibility criteria were included in this systematic review. Results: Nineteen papers were included in the study. The studies were very heterogeneous and reported a comparison of the costs between prenatal versus postnatal repair, the cost of fetoscopic approach versus open surgery, the cost of ventriculoperitoneal shunting (VPS) versus endoscopic third ventriculostomy (ETV), and ETV with choroid plexus cauterization (ETV/CPC), the cost of hospitalization, and the cost of diagnosis for MMC. Conclusion: The results of this study can help in implementing new policies in different countries to assist MC and MMC patients with the cost of treatment and screening.

Meteoropathy: a review on the current state of knowledge.

Meteoropathy is no longer considered a popular myth, but a new disease that significantly impacts daily life, particularly in individuals who experience mental illness, cardiovascular disorders, and respiratory conditions. However, there are very limited data on this condition. This study aimed to comprehensively review and analyze existing in vivo animal studies and human clinical trials investigating the effects of meteoropathy on health and its pharmacological treatment. A thorough literature search was conducted across databases such as PubMed and Scopus to gather relevant information. Our analysis primarily focused on the relationship between meteoropathy and mental health, including the influence on affective temperaments. Additionally, we explored various treatment approaches, emphasizing the combination of muscle exercises, pharmacological interventions, and naturopathy, which have shown promise in alleviating pain among individuals affected by meteoropathy. Future research in meteoropathy should shed light on synthesizing new pharmacological compounds.

Anxiety and depression in geriatric hemodialysis patients: factors that influence the border of diseases.

Introduction: The two main psychological issues that people with end-stage renal disease (ESRD) experience are depression and anxiety. We conducted this study to determine both the prevalence of depression and anxiety, and the factors associated with them, among hemodialysis patients. Methods: Patients aged 18 years or older, who had received hemodialysis in a hemodialysis center in Elbasan, for at least 3 months were included in this study. Beck Anxiety Inventory and Beck Depression Inventory Instruments were used to assess hemodialysis patients levels of depression and anxiety. Results: Overall, 107 hemodialysis patients (men 65.4%) with a mean age of 57 ± 8.9 years were enrolled in the study. The prevalence of anxiety and depression resulted to be 85.98, and 84.11%, respectively. We found a significant difference in depression and anxiety scores in patients age groups of 61-70 years old (OR = 1.8; 95% CI [0.7-3.7]; p = 0.041), in non-smoking patients (OR 3.4; 95% CI [1.09-8.2]; p = 0.04), in diabetic patients (OR 3.4; 95% CI [1.09-8.2]; p = 0.04), and in patients with a time in dialysis of 6-10 years and >11 years, respectively, (OR 3.4; 95% [1.5-9.0]; p = 0.01), (OR1.3; 95% CI [0.4-3.6]; p = 0.04). Conclusion: Our study shows that the prevalence of mental disorders (depression and anxiety) is high among patients with ESRD on maintenance hemodialysis. We recommend a routine screening and referral to psychological health specialists to evaluate the mental health disorders among hemodialysis patients with the primary aim of improving their quality of life.

A review on the role of fatty acids in colorectal cancer progression.

Colorectal cancer (CRC) is the third leading cause of mortality in cancer patients. The role of fatty acids (FA) and their metabolism in cancer, particularly in CRC raises a growing interest. In particular, dysregulation of synthesis, desaturation, elongation, and mitochondrial oxidation of fatty acids are involved. Here we review the current evidence on the link between cancer, in particular CRC, and fatty acids metabolism, not only to provide insight on its pathogenesis, but also on the development of novel biomarkers and innovative pharmacological therapies that are based on FAs dependency of cancer cells.

A Systematic Review on the Role of Arachidonic Acid Pathway in Multiple Sclerosis.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is an inflammatory neurodegenerative disease characterized by destruction of oligodendrocytes, immune cell infiltration and demyelination. Inflammation plays a significant role in MS, and the inflammatory mediators such as eicosanoids, leukotrienes, and superoxide radicals are involved in pro-inflammatory responses in MS. In this systematic review, we tried to define and discuss all the findings of in vivo animal studies and human clinical trials on the potential association between arachidonic acid (AA) pathway and multiple sclerosis. METHODS: A systematic literature search across Pubmed, Scopus, Embase and Cochrane database was conducted. This systematic review was performed according to PRISMA guidelines. RESULTS: A total of 146 studies were included, of which 34 were conducted on animals, 58 on humans, and 60 studies reported the role of different compounds that target AA mediators or their corresponding enzymes/receptors, and can have a therapeutic effect in MS. These results suggest that eicosanoids have significant roles in Experimental Autoimmune Encephalomyelitis (EAE) and MS. The data from animal and human studies elucidated that PGI2, PGFI2α, PGDI2, isoprostanes, PGEI2, PLAI2, and LTs are increased in MS. PLAI2 inhibition modulates the progression of the disease. PGE1 analogues can be a useful option in the treatment of MS. CONCLUSION: All studies reported the beneficial effects of COX and LOX inhibitors in MS. The hybrid compounds, such as COX-2 inhibitors/TP antagonists and 5-LOX inhibitors, can be an innovative approach for multiple sclerosis treatment. Future work in MS should shed light on synthesizing new compounds targeting the arachidonic acid pathway.

ATP-sensitive Potassium Channel Subunits in Neuroinflammation: Novel Drug Targets in Neurodegenerative Disorders.

Arachidonic acids and its metabolites modulate plenty of ligand-gated, voltage-dependent ion channels, and metabolically regulated potassium channels including ATP-sensitive potassium channels (KATP). KATP channels are hetero-multimeric complexes of sulfonylureas receptors (SUR1, SUR2A or SUR2B) and the pore-forming subunits (Kir6.1 and Kir6.2) likewise expressed in the pre-post synapsis of neurons and inflammatory cells, thereby affecting their proliferation and activity. KATP channels are involved in amyloid-ß (Aß)-induced pathology, therefore emerging as therapeutic targets against Alzheimer's and related diseases. The modulation of these channels can represent an innovative strategy for the treatment of neurodegenerative disorders; nevertheless, the currently available drugs are not selective for brain KATP channels and show contrasting effects. This phenomenon can be a consequence of the multiple physiological roles of the different varieties of KATP channels. Openings of cardiac and muscular KATP channel subunits, are protective against caspase-dependent atrophy in these tissues and some neurodegenerative disorders, whereas in some neuroinflammatory diseases, benefits can be obtained through the inhibition of neuronal KATP channel subunits. For example, glibenclamide exerts an anti-inflammatory effect in respiratory, digestive, urological, and central nervous system (CNS) diseases, as well as in ischemia-reperfusion injury associated with abnormal SUR1-Trpm4/TNF-α or SUR1-Trpm4/ Nos2/ROS signaling. Despite this strategy being promising, glibenclamide may have limited clinical efficacy due to its unselective blocking action of SUR2A/B subunits also expressed in cardiovascular apparatus with pro-arrhythmic effects and SUR1 expressed in pancreatic beta cells with hypoglycemic risk. Alternatively, neuronal selective dual modulators showing agonist/antagonist actions on KATP channels can be an option.

Determination of asymmetric dimethyl arginine in human serum by liquid chromatography-tandem mass spectrometry: clinical application in hypertensive subjects.

BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase plays an important role in endothelial dysfunction processes. Recent studies have linked high ADMA levels with several pathological conditions. The interest as a marker of endothelial dysfunction has increased in the last few years. In this paper, a method for serum ADMA quantification by liquid chromatography tandem mass spectrometry has been described. To test the utility in a pathological condition ADMA levels in hypertensive subjects have been measured. METHODS: HPLC separation was performed by hydrophilic interaction chromatography using acetonitrile/water containing 0.1% formic acid and 20 mmol/L ammonium formate. Selected reaction monitoring was performed following the transitions m/z 203.1→46.4 for ADMA and 210.1→46.3 for the internal standard [2H7]ADMA. RESULTS: The method was linear up to 10 µmol/L, limit of detection and limit of quantification were 0.005 µmol/L and 0.01 µmol/L, respectively. Recovery was higher than 96%. Intra- and inter-assay imprecision were lower than 6%. The accuracy, expressed as bias %, was <2.5. ADMA in "healthy" subjects ranged from 0.343 to 0.608 µmol/L and resulted significantly lower than that measured in hypertensive subjects (p<0.001). CONCLUSIONS: The method developed is selective and sensitive, thus suitable not only for research purposes, but also for routinely work.

The Interaction between Arachidonic Acid Metabolism and Homocysteine.

Hyperhomocysteinemia (HHcy) has been considered a risk factor for different diseases, including cardiovascular disease (CVD), inflammation, neurological diseases, cancer, and many other pathological conditions. Likewise, arachidonic acid (AA) metabolism is implicated in both vascular homeostasis and inflammation, as shown by the development of CVD, following the imbalance of its metabolites. This review summarizes how homocysteine (Hcy) can influence the metabolism of AA. In silico literature searches were performed on PubMed and Scopus as main sources. Several studies have shown that altered levels of Hcy, through AA release and metabolism, can influence the synthesis and the activity of prostaglandins (PGs), prostacyclin (PGI2), thromboxane (TXA), epoxyeicosatrienoic acids (EETs), and hydroxyeicosatetraenoic acids (HETEs). It is believed that by targeting Hcy in the AA pathways, novel compounds with better pharmacological and pharmacodynamics benefits may be obtained and that this information is valuable for a dietician to manipulate diets to improve health.

A Systematic Review on the Role of SIRT1 in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a muscular disease characterized by progressive muscle degeneration. Life expectancy is between 30 and 50 years, and death is correlated with cardiac or respiratory complications. Currently, there is no cure, so there is a great interest in new pharmacological targets. Sirtuin1 (SIRT1) seems to be a potential target for DMD. In muscle tissue, SIRT1 exerts anti-inflammatory and antioxidant effects. The aim of this study is to summarize all the findings of in vivo and in vitro literature studies about the potential role of SIRT1 in DMD. A systematic literature search was performed according to PRISMA guidelines. Twenty-three articles satisfied the eligibility criteria. It emerged that SIRT1 inhibition led to muscle fragility, while conversely its activation improved muscle function. Additionally, resveratrol, a SIRT1 activator, has brought beneficial effects to the skeletal, cardiac and respiratory muscles by exerting anti-inflammatory activity that leads to reduced myofiber wasting.

Folic Acid and Autism: A Systematic Review of the Current State of Knowledge.

Folic acid has been identified to be integral in rapid tissue growth and cell division during fetal development. Different studies indicate folic acid's importance in improving childhood behavioral outcomes and underline its role as a modifiable risk factor for autism spectrum disorders. The aim of this systematic review is to both elucidate the potential role of folic acid in autism spectrum disorders and to investigate the mechanisms involved. Studies have pointed out a potential beneficial effect of prenatal folic acid maternal supplementation (600 µg) on the risk of autism spectrum disorder onset, but opposite results have been reported as well. Folic acid and/or folinic acid supplementation in autism spectrum disorder diagnosed children has led to improvements, both in some neurologic and behavioral symptoms and in the concentration of one-carbon metabolites. Several authors report an increased frequency of serum auto-antibodies against folate receptor alpha (FRAA) in autism spectrum disorder children. Furthermore, methylene tetrahydrofolate reductase (MTHFR) polymorphisms showed a significant influence on ASD risk. More clinical trials, with a clear study design, with larger sample sizes and longer observation periods are necessary to be carried out to better evaluate the potential protective role of folic acid in autism spectrum disorder risk.

A simplified method for the determination of total homocysteine in plasma by electrospray tandem mass spectrometry.

Hyperhomocysteinemia is a risk factor for different diseases. Several methods have been developed to analyze homocysteine and the immunometric ones, although expensive, they are in widespread use. A rapid LC-MS/MS method for homocysteine assay has been developed for the application of large clinical chemistry routines. Selected reaction monitoring was performed through the transitions m/z 136.0→90.1 for homocysteine and m/z 140.0→94.0 for the internal standard. ESI was used to generate [H+] adduct ions. Chromatographic isocratic separation was achieved using a strong cation exchange column. The mobile phase was methanol/water (20:80 v/v, containing 0.1% formic acid and 1.5 mmol/L ammonium formate in the water phase) at a flow rate of 0.250 mL/min (35°C). Samples treatment consisted in the reduction with DTT and deproteinization with methanol. Recovery, linearity, LOD, LOQ and total imprecision were evaluated to validate the method. Homocysteine values on 100 serum samples were compared with those obtained by HPLC and immunometric methods. The method is robust, selective and precise in the whole range of values studied. Moreover, low reagent cost and easiness of sample treatment make this method useful, not only for research, but also for routine work.

Medium adsorbance fraction of reticulocyte and myeloperoxidase index may individuate a patient subset with a low risk of chemotherapy-related neutropenia.

In neoplastic patients chemotherapy frequently involves severe myeloid suppression. Sometimes myeloid suppression is the main cause of therapy recycling delay with severe and prolonged neutropenia, anaemia and thrombocytopenia. Our study aimed to verify whether there is a correlation between reticulocyte fractions, reticulocyte indices, myeloperoxidase index (MPXI) and post-chemotherapy myelopoietic function and severe post-chemotherapy neutropenia. A cohort of 112 patients was identified, 30 with lymphoma or myeloma and 82 with solid neoplasms with bone marrow micrometastases. The patients were treated with chemotherapy (CT). After CT, 60 patients had neutropenia (ANC <500/mcl) for a median of 7 days (range 3-21). Before CT, myelopoietic function was assessed by the above-mentioned parameters using a hematologic automated analyzer. We assigned patients with an MPXI-positive value and medium adsorbance fraction of reticulocyte (MFR) >10.7% a score of 1, and a score of 0 was assigned to the remaining patients. Patients with a score of 1 showed a lower number of neutropenic events (only 9 out of 36 patients) than those with a score of 0 (51 out of 76 patients), p<0.0001. MPXI and MFR may be used in the assessment of myelopoiesis before CT administration, independently of the type of tumor, CT regimen and number of CT cycle, with the aim of identifying a patient subset with a lower risk of developing neutropenia post-CT.

Detection of 14 human papillomavirus genotypes in cervical samples in women from a central-southern area of Italy showing different Pap test results.

We evaluated the prevalence of human papillomavirus (HPV) infection and correlated the molecular test results with the cytological examination data (PAP test) in 364 women living in central-southern Italy (Molise region), by means of polymerase chain reaction HPV DNA genotyping and of cervical cytology. One hundred and twenty-eight women resulted HPV positive (35.2%), HPV16 being the most frequent genotype. HPV positive women were significantly younger than negative patients (35.9 +/- 8.4 years and 38.2 +/- 9.1, respectively; p = 0.018); women with multiple infections were also significantly younger than those with single infection (31.7 +/- 6.9 and 37.6 +/- 8.3, respectively; p = 0.0002). Moreover, high risk HPV positive patients were significantly younger than low risk HPV positive women (35.1 +/- 7.7 and 40.5 +/- 10.5, respectively; p = 0.008). In the HPV positive group, 14 patients (10.9%) did not show any significant cytological alteration. Conversely, 7 out of 236 HPV negative women (3.0%) showed high grade squamous intraepithelial lesions (HSIL). Furthermore, HPV 16 or 18 were present in more than 70% of women positive for HSIL at cytology. Our data suggest the potential effectiveness of combined cytology and molecular test for further study of clinical cases with apparently laboratory conflicting results.

Salivary thiols and enzyme markers of cell damage in periodontal disease.

OBJECTIVES: Recent studies describe the potential use of biochemical markers in the evaluation of the severity of periodontitis; moreover, patients suffering from periodontitis frequently complain of halitosis (breath malodour), mainly depending on volatile compounds (e.g. hydrogen sulphide, methyl mercaptan, etc.) produced by anaerobic metabolism of oral bacteria and involving sulphur-containing amino acids. In this study, salivary sulphur compounds, such as cysteine, cysteinylglycine and glutathione and some markers of cellular damage (lactate dehydrogenase and aspartate amino transferase), were measured in periodontitis patients and correlated with the periodontal probing pocket's depth. DESIGN AND METHODS: Twenty-two periodontitis patients and forty control subjects were studied for the salivary activities of lactate dehydrogenase and aspartate aminotransferase and cysteine, cysteinylglycine and glutathione concentrations. The periodontitis patients were divided into two subgroups based on the severity of periodontal disease, expressed as median periodontal probing pocket depth (> or <5 mm). Enzyme activities were measured by using an automated clinical analyzer; cysteine, cysteinylglycine and glutathione concentrations were measured by HPLC equipped with fluorescence detector. RESULTS: A statistically significant increase of the salivary parameters level (cysteine, cysteinylglycine, glutathione, aspartate aminotransferase and lactate dehydrogenase) was found in the patient subgroup with periodontal probing pocket depth >5 mm, the salivary cysteine concentrations showing the most significant correlation. CONCLUSIONS: Salivary cysteine, a direct precursor of hydrogen sulphide, could be considered reliable markers for the oral tissue damage severity in periodontitis patients.