Intensity and pleasantness of sucrose taste in patients with winter depression.

OBJECTIVES: Increased consumption of carbohydrates and craving for sweets are considered core features of winter depression. Unfortunately, little is known about neural and behavioral correlates of these symptoms. The primary aim of the present study was to evaluate taste responses to sucrose solutions in depressed patients with seasonal affective disorder (SAD). METHODS: Intensity and pleasantness ratings of sucrose solutions, electrogustometric thresholds, and taste identification abilities were assessed in depressed patients with SAD and non-seasonal affective disorder (non-SAD), and in non-depressed controls. RESULTS: Electrogustometric thresholds and identification abilities did not differ between the study groups. There were no differences between the groups in intensity or pleasantness ratings of sucrose solutions (1-30%). The proportion of 'sweet likers', i.e. subjects rating the highest sucrose concentration as most pleasant, was similar in the controls, SAD, and non-SAD patients. DISCUSSION: The present results suggest that: (i) winter depression is not associated with major alterations in gustatory function; and (ii) sweet craving and increased consumption of carbohydrates in patients with winter depression is not secondary to altered responses to sweet tastants. More studies are needed to characterize hedonic responses of patients with SAD to other sweet and non-sweet foods.

Mitochondrial NADH-dehydrogenase subunit 3 (ND3) polymorphism (A10398G) and sporadic breast cancer in Poland.

Mitochondria are subcellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, but very few reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients compared to healthy control populations. Here we report the abundance of the 10398G polymorphism in a Polish breast cancer population and its frequency in controls. Amongst individuals with breast cancer the G single nucleotide polymorphism (SNP) is present in 23% of affected females compared to 3% of controls. This difference is highly statistically significant (P = 0.0008). It is therefore possible that the 10398G SNP constitutes an inherited predisposition factor for the development of breast cancer.

Molecular oncology focus - is carcinogenesis a 'mitochondriopathy'?

Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources of data for systematic review, meta-analysis, or finally for establishment of clinically applicable markers. In this review technical and conceptual errors commonly occurring in the literature are summarized. In the first place we discuss, why many of the published papers cannot be used as a valid and clinically useful sources of evidence in the biomedical and healthcare contexts. The reasons for introduction of noise in data and in consequence - bias for the interpretation of the role of mitochondrial DNA in the complex process of tumorigenesis are listed. In the second part of the text practical aspects of mtDNA research and requirements necessary to fulfill in order to use mtDNA analysis in clinics are shown. Stringent methodological criteria of a case-controlled experiment in molecular medicine are indicated. In the third part we suggest, what lessons can be learned for the future and propose guidelines for mtDNA analysis in oncology. Finally we conclude that, although several conceptual and methodological difficulties hinder the research on mitochondrial patho-physiology in cancer cells, this area of molecular medicine should be considered of high importance for future clinical practice.

Mitochondrial genotype in vulvar carcinoma - cuckoo in the nest.

Vulvar squamous cell carcinoma (VSCC) is a rare female genital neoplasm. Although numerous molecular changes have been reported in VSCC, biomarkers of clinical relevance are still lacking. On the other hand, there is emerging evidence on the use of mtDNA as a diagnostic tool in oncology. In order to investigate mtDNA status in VSCC patients, haplogroup distribution analysis and D-loop sequencing were performed. The results were compared with available data for the general Polish population, cancer free-centenarians as well as patients with endometrial and head and neck cancer. The obtained data were also compared with the current status of mitochondrial databases. Significant differences in haplogroup distribution between VSCC cohort, general Polish population and cancer-free centenarians cohort were found. Moreover, a correlation between the VSCC patients haplogroup and HPV status was observed. Finally, a specific pattern of mtDNA polymorphisms was found in VSCC. Our results suggest that the mitochondrial genetic background may influence the risk of VSCC occurrence as well as susceptibility to HPV infection.

[Predictors of smoking cessation after stroke]. / Predyktory rzucania palenia po udarze mózgu.

Cigarette smoking is a major modifiable risk factor for stroke. Smoking dose dependently increases the risk of stroke, especially in patients below 75 years of age. Although smoking cessation is considered as one of the most effective methods of secondary stroke prevention, little is known about nicotine dependence and predictors of smoking cessation after stroke. Identification of such predictors could facilitate the development of anti-smoking interventions in post-stroke patients. Results of previous studies showed that smoking cessation is determined by the interplay of multiple factors, including sociodemographic (gender, age, race, living conditions, employment), clinical (functional status), psychobiological (nicotine dependence, depressed mood) and environmental (smoking household members) factors. Limitations of most studies were relatively small sample sizes and lack of verification of smoking status with a biochemical marker (e.g. expired CO). The aim of this article is to summarize current knowledge about predictors of smoking cessation after stroke.

Post-session injections of a protein synthesis inhibitor, cycloheximide do not alter saccharin self-administration.

A large body of evidence indicates that reactivation of aversive memories leads to protein synthesis-dependent memory reconsolidation which can be disrupted by cycloheximide (CHX) and other protein synthesis inhibitors. The aim of the present study was to investigate whether CHX would alter maintenance of well-trained instrumental responding for 0.1% saccharin. Male Wistar rats were trained to lever press for saccharin. When lever pressing stabilized, experimental self-administration sessions with CHX (3 mg/kg, s.c.) started. The animals received four experimental sessions, with each session separated by 5 days. The protein synthesis inhibitor was injected immediately after the experimental sessions 1-3. Repeated post-session injections of CHX did not alter saccharin self-administration. A two-bottle choice test conducted after the last experimental session revealed that CHX had not induced any conditioned taste aversion to 0.1% saccharin. The present results suggest that well-consolidated long-term memory of an appetitive instrumental task does not depend on de novo protein synthesis.

[Metabolic markers of the head and neck cancers--clinical applications and the biochemical background]. / Markery metaboliczne nowotworów glowy i szyi--aplikacje kliniczne i podloze biochemiczne.

The problem of diagnosis in the field of head and neck region is still valid. Specific diagnosis and precise estimation of the tumor's size with the use of CT and MRI imaging is generally unsatisfactory. The Positron Emission Tomography (PET) supports this process with additional information about the tumor's metabolism. Numerous publications show that PET-CT has a great influence on the evaluation of the size of the tumor, presence of lymph node metastases, choice of treatment and the prognosis of the recurrence. Cancer cells represent a specific metabolic state. These cells intake large quantities of glucose and utilize it in the process of glycolysis. The oxidative phosphorylation is not efficient in the transformed cells and defects in mitochondrial functions are at the heart of malignant cell transformation. Disruption of the oxidative phosphorylation chain has been described in the neoplasms. As a consequence, in cancer the glycolysis is active even in the normoxic environment. This metabolic shift in cell transformation has been described in early XX century and so called Warburg's hypothesis profoundly influenced the present perception of cancer metabolism, positioning what is termed aerobic glycolysis in the mainstream of clinical oncology. Today we know that neoplastic cells differ at the proteomic level. A subset of different proteins such as hexokinase II or HIF are upregulated. These abnormalities might be used as the neoplastic markers.

A protein synthesis inhibitor, cycloheximide does not alter cue-induced reinstatement of saccharin seeking.

A large body of evidence indicates that reactivation of aversive memories leads to protein synthesis-dependent memory reconsolidation which can be disrupted by cycloheximide and other protein synthesis inhibitors. The aim of the present study was to investigate whether cycloheximide would alter reconsolidation of the associations involving discrete cues paired with a sweet reward in an appetitive instrumental task. Rats trained to lever press for 0.1% saccharin were repeatedly tested for cue-induced reinstatement of non-reinforced responding for saccharin. CHX (3 mg/kg, s.c.) or its vehicle was injected immediately after each reinstatement session. The protein synthesis inhibitor did not alter the ability of the saccharin-paired cues to reinstate saccharin seeking. The present results suggest that passive re-exposure to saccharin-paired discrete cues in the reinstatement procedure does not lead to any cycloheximide-sensitive reconsolidation of the original associations.

Depressive symptoms and olfactory function in older adults.

AIMS: Neuroimaging studies suggest a significant overlap between brain regions involved in the regulation of olfaction and mood. The aim of the present study was to search for correlations between depressive symptomatology measured by the 15-item Geriatric Depression Scale (GDS) and olfactory function assessed with Sniffin' Sticks in non-demented older adults (aged 53-79 years). METHODS: Taste detection thresholds were also measured by means of electrogustometry on the anterior tongue. RESULTS: No correlation was found between the GDS scores (range: 0-12) and olfactory thresholds or olfactory identification scores. Similarly, there was no relationship between depressive symptoms and electrogustometric thresholds. Subjects (n = 25) scoring > or = 5 on the GDS were classified as 'depressed' and all other individuals (n = 60) were classified as 'non-depressed'. The two groups did not differ in terms of the olfactory measures and electrogustometric threshold. CONCLUSION: Depressive symptoms are not associated with any major olfactory deficit in non-clinical older adults.

Misuse of xylometazoline nasal drops by inhalation.

Six male prisoners who misused xylometazoline nasal drops by inhalation were interviewed by a prison physician in 2006. The prisoners received xylometazoline drops during regular visits in the prison ambulatory service. In order to get the medication, the subjects reported false symptoms of rhinosinusitis and allergic reactions. Psychoactive effects of inhaled xylometazoline were described as "stimulation," "excitation," and "feeling of strength." Although preliminary, our findings suggest that topical adrenergic decongestants can produce rewarding effects when administered by inhalation.

[Molecular biology of endometrial carcinoma]. / Biologia molekularna i diagnostyka raka endometrium.

Endometrial carcinoma is among the most frequently diagnosed gynecological malignancies in highly developed countries. Research has been conducted for 20 years to define the molecular pathology of this disease and much is already known, but adequate prognostic, diagnostic, and monitoring markers are still missing. Recently, mitochondrial research opened a new perspective. The participation of abnormalities of those organelles and mutations of the mitochondrial genome has been defined in some types of cancer and is still under investigation. MtDNA mutations are also found in endometrial adenocarcinoma, although their impact on cell physiology has not been determined so far. Some processes involving mitochondria are widely known and described in numerous papers. These include electron transport and apoptosis, but others await further research. A forward genetics approach has been used in a wide spectrum of projects in which cancer tissue samples were collected from subjects with defined diagnoses and metabolic abnormalities and mtDNA mutations were checked. Thanks to this approach, characteristic patterns of mitochondrial disruption have been assigned to specific types of cancer. This review focuses on the molecular characteristics of endometrial adenocarcinoma with special focus on mitochondrial abnormalities. Research on cancer molecular pathology in endometrial adenocarcinoma may lead to the development of specific screening and/or diagnostic markers.

[The impact of mtDNA mutations on proteins structure in selected types of cancer]. / Wystepowanie mutacji w mtDNA i ich potencjalyn wplyw na strukture bialek w wybrancych typach nowotworów.

Recently published papers report a large number of mitochondrial DNA mutations in many different cancer types, but their significance for electron transport chain proteins remains unknown. This review covers structural mutations of mitochondrial genes, choosing prostate cancer, esophageal cancer and epithelioma as research models. As all mitochondrial genes encode subunits of the electron transport chain, the review focuses on the consequences of structural mutations on cell metabolism.

[Mitochondrial DNA mutations in the pathogenesis in the head and neck squamous cell carcinoma]. / Mutacje mitochondrialnego DNA w rozwoju nowotworów glowy i szyi.

Data reported until today suggested a pivotal role of nuclear DNA mutations in the process of carcinogenesis. Recently more and more authors claim that disruption of mitochondrial DNA should not be excluded from this analysis. mtDNA have been reported in many cancers of head and neck region. Mitochondrial D-loop has been proven to be mutation hot - spot with majority of mutations in the positions 303 to 315 of poly-C tract. Data show that 37% of patients with premalignant lesions and 62% with carcinoma in situ are positive for mtDNA mutations. Moreover mutations in genes encoding ND2, ND5, COIII, CYTB, and ATP6 were observed in 17% of patients. Mutations in mitochondrial rRNA genes occured in similar number of cases. Neoplastic cells undifferentiation and disease progression is accompanied by multiplication of mtDNA number and increased mtDNA content. mtDNA content corellates with the stage of the disease. mtDNA mutations faciliate cell proliferation and inhibit apoptosis by increasing the production of ractive oxygen species (ROS). Cells harbouring mutated mtDNA have increased proliferation rate, as increased ROS concentration may act as an endogenous growth factor.

Nicotine-induced conditioned taste aversion in the rat: effects of ethanol.

It has been shown that small doses of ethanol antagonise the discriminative stimulus properties of nicotine in the rat. The aim of the present study was to evaluate whether ethanol could antagonise the aversive stimulus effects of nicotine. Wistar rats were trained to associate nicotine injections with a novel tasting fluid (0.1% saccharin) in the conditioned taste aversion procedure. Nicotine (0.3 mg/kg, s.c.) was injected 5 min after the end of a 20-min exposure to the saccharin solution. Ethanol (0.25-0.5 g/kg, i.p.) was administered 5 or 50 min before nicotine. In general, ethanol did not inhibit nicotine-induced conditioned taste aversion. Contrary to the findings in drug discrimination studies, a slight but significant enhancement of nicotine-induced taste aversion conditioning was observed after ethanol pre-treatment. Blood ethanol levels were measured in a separate group of rats. Maximal blood ethanol levels after i.p. administration of 0.25 or 0.5 g/kg ethanol exceeded 20 and 80 mg%, respectively. Concluding, the present results may indicate that ethanol does not attenuate nicotine-induced conditioned taste aversion in the rat.

[Olfactory neuroblastoma (esthesioneuroblastoma): etiopatogenesis, diagnosis, and treatment]. / Neuroblastoma nerwu wechowego (esthesioneuroblastoma): etiopatogeneza, diagnostyka i leczenie.

INTRODUCTION: Esthesioneuroblastoma is a malignant tumour arising from the olfactory epithelium located in the upper part of the nasal cavities. Recent clinical and preclinical studies shed more light on etiopathogenesis, diagnosis, and treatment of this rare malignancy. MATERIAL AND METHODS: A systematic review of PubMed/Medline and available Polish literature. RESULTS: Molecular studies indicate basal progenitor cells of the olfactory epithelium as the origin of esthesioneuroblastoma. Tumour symptoms are related to its location and typically include: epistaxis, nasal obstruction, olfactory and ophtalmic disturbances as well as craniofacial pain. Esthesioneuroblastoma should be differentiated from embryonic rhabdomyosarcoma, Ewing's sarcoma, melanoma, lymphoma, and pericytoma. A combination of surgery and radiotherapy seems to be the optimum approach to treatment. More aggressive treatment regimens are promising but require further studies. CONCLUSIONS: Esthesioneuroblastoma is a rare malignant tumour arising from the olfactory epithelium. Early diagnosis and interdisciplinary approach to treatment is vital in the management of the tumour.

Readiness Visual Analog Scale: A Simple Way to Predict Post-Stroke Smoking Behavior.

BACKGROUND AND PURPOSE: The aim of the present study was to assess a relationship between readiness to quit and post-stroke smoking behavior. METHODS: Eighty-six active smokers with first-ever ischemic stroke were recruited in a tertiary-care stroke unit. The question "Are you ready to quit smoking within the next month?" with yes/no responses and the 10-cm readiness visual analog scale (VAS) was administered during the anti-smoking intervention. Smoking status was verified at the 3- and 12-month follow-up. RESULTS: The readiness VAS score at hospitalization was significantly lower in patients classified as smokers as compared to patients classified as non-smokers. The readiness score <5 cm was a significant predictor of smoking at the 3-month (OR, 7.3) and 12-month follow-up (OR, 4.9). CONCLUSIONS: The present results suggest that the readiness VAS can be used as a simple and inexpensive instrument for early identification of patients who continue to smoke after stroke.

Taste function in methadone-maintained opioid-dependent men.

It has been shown repeatedly that opioid dependence is associated with increased consumption of refined sugars. It is possible that this association results from altered taste reactivity in opioid-dependent subjects. Thus, in the present study, we compared taste responses to sweet, bitter, sour and salty solutions in methadone-maintained opioid-dependent men and healthy control subjects. The two groups did not differ in terms of rated intensity or pleasantness of sucrose (1-30%), quinine (0.001-0.005%), citric acid (0.02-0.1%) and sodium chloride (0.18-0.9%) solutions. Proportions of 'sweet-likers', i.e. subjects rating a 30% sucrose (0.88 M) solution as the most pleasant, were also similar in both groups. In line with the previous findings, the methadone-maintained subjects reported adding more table sugar to caffeinated beverages. The results of the present study suggest that changes in taste reactivity may not be responsible for altered dietary choices in opioid addicts.

Depressive symptoms and taste reactivity in humans.

Animal studies suggest that induction of depression-like states may alter preference for sweet tastants. A major goal of the present study was to search for correlations between depressive symptoms measured by the Beck Depression Inventory (BDI) and taste responses to sweet and bitter substances. Thirty-three nonclinical volunteers rated intensity and pleasantness of chocolate and vanilla milk as well as of sucrose- and quinine-soaked filter paper disks. Reactivity to citric acid (sour) and sodium chloride (salty) was also tested with the paper disk methodology. Taste detection thresholds were assessed by means of electrogustometry. A weak inverse relationship was found between the BDI scores (range: 3-33) and rated intensity of paper disks soaked in 60% sucrose. No correlations were found between depressive symptoms and intensity, pleasantness or identification of the other samples. Similarly, there was no relationship between the BDI scores and responses to chocolate and vanilla milk. BDI scores were not associated with electrogustometric thresholds. These data suggest that depressive symptoms may not influence taste reactivity in nonclinical population.

Dissociation of ethanol and saccharin preference in fosB knockout mice.

The Fos family of transcription factors may play a key role in various forms of brain plasticity. Among different genes coding Fos proteins is the fosB gene. Protein products of the fosB gene are thought to be critically involved in neural adaptations produced by chronic treatment with drugs of abuse. fosB gene transcription leads to accumulation of full-length FosB as well as its truncated form, deltafosB. Stable isoforms of deltafosB called chronic FRAs accumulate in the brain after chronic administration of various drugs of abuse. The purpose of the present study was to evaluate the role of the fosB gene in two-bottle choice ethanol self-administration. For this aim, ethanol (2-8% v/v) intake and preference was assessed in fosB mutant (n=17) and wild-type (WT) mice (n=16). For comparison, consumption of saccharin (0.05-0.8% w/v) and quinine (15-960 microM) solutions was assessed in the same animals. Ethanol preference in both groups varied from around 50% for the lowest to 20% for the highest ethanol concentration. Neither ethanol intake (g/kg) nor preference differed between the two genotypes. In contrast, saccharin preference, but not intake, was higher in the fosB mutants. Only slight and inconsistent between-group differences were observed in terms of quinine preference. The present results suggest that permanent elimination of fosB gene products does not alter ethanol intake but may enhance preference for sweet solutions in mice.