An Overview of Bcl-2 Expression in Histopathological Variants of Basal Cell Carcinoma, Squamous Cell Carcinoma, Actinic Keratosis and Seborrheic Keratosis

The Bcl-2 protein has been shown to suppress cell death and protects cell against apoptosis induced by different death-inducing signals. In this study the authors have analyzed imunohistochemically the expression of Bcl-2 protein in the histopathological variants of the most common malignant tumors of the skin – basal cell carcinoma (BCC) and squamous cell tumor (SCC), as well as in the precancerous lesion actinic keratosis (AK) and in benign tumor seborrheic keratosis (SK). Bcl-2 expression in solid, adenoid and cystic variants of BCC exhibited immunoreactivity of tumor stroma with more intense staining among peripheral palisading cells. Morphoeic variant demonstrated reduced amount of Bcl-2 expression. Among SCC in all samples, tumor tissue lack to express Bcl-2 positivity. In cases of hypertrophic and atrophic variants of AK, Bcl-2 expression was confined to basal cell layer, as well as in one case of hypertrophic variant in suprabasal cells. In three histological variants of SK expresseion of Bcl-2 protein was in areas of basaloid proliferation, while in areas of squamous differentiation was negative. In clonal variant immunostaining was positive among cells in characteristic »nests« Distribution of Bcl-2 protein expression in solid, adenoid and cystic variant of BCC showed that peripheral proliferating cells are protected against apoptosis what permits tumor growth. In morpheaform variant reduced amount of Bcl-2 expression indicated that this variant of BCC has increased cell proliferation, and in practice shows tendency for recurrence and difficulties to eradicate. Bcl-2 expression supports the observation that tumor cells are derived from basal keratinocytes. In SCC, lack of Bcl-2 expression indicates that origin of tumor cells is from more differentiated suprabasal keratinocytes. In AK results suggest that immunoreactivity is regulated with respect of the keratinocyte’s differentiation status, but not closely correlate with proliferative rate

Modern Approach to Topical Treatment of Aging Skin

The main processes involved in skin aging are intrinsic and extrinsic. Apart from them, so called stochastic aging connotes cell damage caused by metabolic processes, free radicals and cosmic irradiation. The clinical expression of intrinsic aging include smooth, dry, and thinned skin with accentuated expression lines. It is inevitable and time dependent. Extrinsically aged skin shows signs of photodamage which include appearance of wrinkles, pigmented lesions, actinic keratoses and patchy hypopigmentations. Therapeutic modalities imply photoprotection with sunscreens that prevent sunburns and block ultraviolet irradiation. Other modalities include use of retinoids which regulate gene transcription with subsequent cellular differentiation and proliferation. The topical and peroral administration of »network antioxidants» such as vitamin E and C, coenzyme Q10, alpha-lipoic acid and glutathione, enhance antiaging effect. The other antioxidants such as green tea, dehydroepiandrosterone, melatonin, selenium and resveratrol, have also antiaging and anti-inflammatory effects. Topical bleaching agents such as hydroquinone, kojic acid and azelaic acid can reduce signs of aging. Studies confirm the efficacy of these topical agents in combination with superficial and/or medium depth or deep peeling agents for photodamaged skin treatment. Indications for type of chemical peels according to various clinical diagnosis are done, as well as advantages and disadvantages of differetn types of chemical peels

Modern Approach to Topical Treatment of Aging Skin

The main processes involved in skin aging are intrinsic and extrinsic. Apart from them, so called stochastic aging connotes cell damage caused by metabolic processes, free radicals and cosmic irradiation. The clinical expression of intrinsic aging include smooth, dry, and thinned skin with accentuated expression lines. It is inevitable and time dependent. Extrinsically aged skin shows signs of photodamage which include appearance of wrinkles, pigmented lesions, actinic keratoses and patchy hypopigmentations. Therapeutic modalities imply photoprotection with sunscreens that prevent sunburns and block ultraviolet irradiation. Other modalities include use of retinoids which regulate gene transcription with subsequent cellular differentiation and proliferation. The topical and peroral administration of »network antioxidants» such as vitamin E and C, coenzyme Q10, alpha-lipoic acid and glutathione, enhance antiaging effect. The other antioxidants such as green tea, dehydroepiandrosterone, melatonin, selenium and resveratrol, have also antiaging and anti-inflammatory effects. Topical bleaching agents such as hydroquinone, kojic acid and azelaic acid can reduce signs of aging. Studies confirm the efficacy of these topical agents in combination with superficial and/or medium depth or deep peeling agents for photodamaged skin treatment. Indications for type of chemical peels according to various clinical diagnosis are done, as well as advantages and disadvantages of differetn types of chemical peels

Fractionated Illumination Improves the Outcome in the Treatment of Precancerous Lesions with Photodynamic Therapy

Photodynamic therapy (PDT) is a noninvasive therapy for non-melanoma skin cancer. The aim of this study was comparison of efficacy between fractioned versus single dose illumination in photodynamic therapy (PDT) of actinic keratosis (AK) and Bowen’s disease (BD). Fifty-one patients (36 AK and 15 BD) were treated with PDT. They were randomly arranged in two treatment groups. Group one included 26 patients (20 AK and 6 BD) that, after five hours of incubation with 20% 5-ALA, were treated with a single illumination of 100 Jcm–2 at fluence rate of 30 mWcm–2. Group two included 25 patients (16 AK and 9 BD) that, after 16 hours of incubation with 20% 5-ALA, were treated with two light fractions (50 plus 50 Jcm–2) at same fluence rate with dark interval of two hours between fractions. Twenty-four weeks later, a treated area was incubated for four hours again with 5-ALA in order to detect occult areas of abnormal skin with possible remaining tumor tissue. In case of fluorescence, histological examination was performed. In the group one, fluorescence at the end of the session was absent in 19 (73%) or very weak in 7 (27%). Residual tumor was found in 15 (75%) AK and in 4 (66.6%) BD. In the group two, fluorescence at the end of second session was more intense; in one patient (4%) was absent, very weak in 5 (20%) and weak in 19 (76%) of patients. In this group histology revealed remaining tumor tissue in only 2 (12.5%) AK and 2 (22.2%) BD. Among the patients in the first group, the remaining tumor tissue was significantly bigger (p=0.005). The treatment response with clearing of tumor tissue was significantly higher in fractionated illumination than in a single dose illumination group. Fractionated illumination scheme with 16 hours of incubation separated by two hours dark interval significantly improves the therapeutic outcome in tumor eradication

Specific and Gender Differences between Hospitalized and out of Hospital Mortality due to Myocardial Infarction

In this paper, the authors evaluate gender related differences of myocardial infarction mortality before and after hospital admittance. Myocardial infarction mortality in the Clinical Hospital Split in the seven years period between 2000 and 2006, have been analyzed together with out of hospital sudden death patients with acute myocardial infarction established during autopsy. During the seven year period between 2000 and 2006, 3434 patients were treated for myocardial infarction in the Split Clinical Hospital, 2336 (68%) males and 1098 (32%) females with a 12% total mortality (427 patients). The annual number of hospitalized persons has been increasing during that period (474 in yr. 2000 vs. 547 in yr. 2006), while mortality decreased from 15% in 2000 to 9.6% in 2006. Female patients had significantly higher hospital mortality than male patients, (228 or 21% vs. 202 or 9%, p<0.05). Women also had significantly higher total AMI mortality (23.7% vs. 15,7%, p<0.05). Anterior myocardial infarction with ST elevation in precordial leads had significantly higher mortality (19%) compared to patients with lateral (11%), inferior (10%) myocardial infarction with ST elevation and also NSTEMI (4%) mortality p<0.05. Female patients more frequently die in hospital, 84% (230) than out of hospital 16% (43). From the total number of AMI deaths (388) in male patients, 56% (217) were in hospital and 44% (171) out of hospital (p<0.001). Men had significantly higher prehospital mortality rate than women (81% vs. 19%, p<0.05). Men also more frequently died from ventricular fibrillation (22% vs. 10%, p<0.05), while women died more frequently of heart failure, cardiogenic shock, and myocardial rupture (33% vs. 15% p<0.05). Regarding the total number of deaths from myocardial infarction men had significantly higher prehospital mortality compared to women (178 or 7.3% vs. 43 or 3.7%, p<0.05). Anterior myocardial infarction had a significantly higher rate in patients dying pre-hospital (58%), in contrast to inferior (36%) and lateral myocardial infarction with ST elevation (6%) p<0,05.We have concluded that male patients die more frequently within the first few hours of AMI mostly due to malignant arrhythmias, while female patients died in sub acute stage due to heart failure while being hospitalized. Nevertheless total mortality of AMI remains significantly higher in women

The Epidemiology of Non-Traumatic Prehospital Sudden Death in Split-Dalmatia County

The aim of this study was to determine epidemiology of non-traumatic prehospital sudden adult deaths in Split- -Dalmatia County from 2000. to 2005. The following information were collected from autopsy reports in the archives of University Hospital Split: gender of deceased, birth date, date of death, location of death, immediate cause of death, previously diagnosed diseases that might lead to terminal outcome. There were 160 non-traumatic prehospital sudden adult deaths in the observed period, with 104 (65%) male and 56 (35%) female autopsies performed. Diseases of cardio- vascular system were the main cause of death, responsible for 95 (59.37%) sudden deaths, followed by diseases of respira- tory system (14.37%) and central nervous system (8.12%). The most frequent cause of non-traumatic sudden death was myocardial infarction, found in 50 cases. July and September were the months of the most frequent occurrence of sudden death. In this study it was confirmed that sudden death incidence increases with age, with almost half of all deaths occurring in people between ages of 61–80. The result that a fifth of all sudden deaths occurred in people aged 51–60 is troubling and potentially preventable. The most frequent location of death was deceased’s place of residence (N=29), followed by the ambulance vehicle (N=17). In conclusion, this is the first publication describing the incidence of pre- hospital sudden non-traumatic adult death in Split-Dalmatia County. Causes of sudden death and its incidence are in accordance with World Health Organization’s information on general causes of death in Croatia and Western Europe

Razlike u izražaju bjelančevina-regulatora apoptoze i proliferacije između zdrave kože i kože bolesnika s kroničnim bubrežnim zatajenjem i svrbežom

Svrbež je česta pojava u dijaliziranih bolesnika s kroničnim zatajenjem bubrega. U cilju istraživanja mogućih uzroka svrbeža u tih bolesnika, istraženo je 12 uzoraka kože uzete s bedra dijaliziranih bolesnika sa svrbežom i 5 uzoraka kože zdravih ispitanika. U histološkim rezovima navedenih uzoraka tkiva kože izmjerena je debljina epidermisa, a podatci su statistički obrađeni. Rezovi tkiva imunohistokemijski su obojani biljezima proliferacije Ki-67, antiapoptotskim biljegom Bcl-2, proapoptotskim biljezima Bax i kaspaza-3, a primijenjena je i TUNEL metoda za dokazivanje stanične smrti ili apoptoze. Naše je istraživanje pokazalo u kontrolnoj zdravoj koži proliferacijski indeks od 10.8 %, dok je u koži dijaliziranih bolesnika proliferacijski indeks bio 11.8 % nakon tri godine na dijalizi te 12.5 % nakon 5 godina dijalize. Navedeni rezultati ukazuju na povećani proliferacijski indeks u koži bolesnika na dijalizi te njegovu povezanost s trajanjem dijalize. Statistička analize mjesta stanične proliferacije u bazalnom i suprabazalnim slojevima, ukazala je da je u zdravih ispitanika proliferacija bila smještena ponajprije u bazalnom sloju dok je u dijaliziranih bolesnika uočen pad stanične proliferacije u bazalnom i suprabazalnom sloju nakon tri godine dijalize u odnosu na kožu zdravih ispitanika. Značajan pad proliferacije u suprabazalnim slojevima uočen je nakon pet godina dijalize u odnosu na kožu zdravih ispitanika kao i kožu dijaliziranih bolesnika nakon tri godine. Prosječna debljina epidermisa kože zdravih ispitanika iznosila je 53 μm, a u dijaliziranih bolesnika od 23 do 34 μm tijekom 3-5 godina trajanja dijalize. Ravnoteža između Bcl-2 i Bax bjelančevina nije se značajno promijenila u epidermisu dijaliziranih bolesnika nakon tri godine dijalize, u usporedbi s epidermisom kože zdravih ispitanika. Nakon petogodišnjeg razdoblja dijalize, uočen je pojačani izražaj proapoptotske Bax bjelančevine, a smanjeni izražaj antiapoptotske Bcl-2 bjelančevine u bazalnom i nazubljenom sloju epidermisa, kao i prisutnost apoptotskih stanica (TUNEL i kaspaza-3 pozitivnih) u površinskom i nazubljenom sloju epidermisa bolesnika sa svrbežom. Naše istraživanje dokazalo je prevladavanje proapoptotske Bax bjelančevine u odnosu na antiapoptotsku Bcl-2 bjelančevinu, kao i prisutnost apoptotskih stanica u dubljim slojevima epidermisa u bolesnika na dugotrajnoj dijalizi. Pretpostavljamo kako bi stanjenje epidermisa u tih bolesnika moglo biti povezano s pojavom apoptotskih stanica u dubljim epidermalnim slojevima, dok bi promjena unutarnje ravnoteže između stanica epidermisa mogla utjecati na živčane završetke smještene u epidermisu, s posljedičnim nastanka svrbeža.Chronic renal failure is often associated with skin itching (pruritus) in dialyzed patients. In order to investigate the possible causes of pruritus in those patients, the epidermis of the thigh of 12 dialyzed patients and 5 controls from patients without renal disease were examined. The sections of the epidermis were measured and statistically analyzed, and were immunohistochemically stained using antibodies to proliferation marker Ki-67, anti-apoptotic marker Bcl-2, and pro-apoptotic markers Bax and caspase-3, as well as TUNEL method. Proliferation index of epidermal cells was 10.8 % in normal skin, 11.3 % in the skin of patients after 3 years of dialysis and 12.5 % after 5 years of dialysis. An increased proliferation index characterized the skin of patients on dialysis, and accorded with duration of dialysis. After 3 years period on dialysis, a moderate increase of basal layer cell proliferation was noted in patient’s epidermis, while a significant decrease of proliferation in suprabasal layer of epidermis characterized patients after 5 years on dialysis. While the mean thickness of normal epidermis was 53 μm, in dialyzed patients it ranged between 23 and 34 μm during the 3–5 year period on dialysis. Compared to normal skin, the fine balance between the Bcl-2 and Bax proteins did not greatly change in the epidermis of dialyzed patients during the three years of dialysis. Following five-year dialysis, the epidermis displayed increased Bax and decreased Bcl-2 expression in the basal and intermediate epidermal layers, as well as the presence of apoptotic cells (TUNEL and caspase-3 positive) both in the superficial and intermediate epidermal layers. Our study demonstrated the predominant expression of cell death Bax proteins over cell survival Bcl-2 proteins, and apoptotic cells in the deeper layers of the epidermis in patients on long-term dialysis. We speculate that the thinning of the epidermis might be associated with the appearance of dead cells in the deeper epidermal layers, while the changed internal milieu of epidermal cells could possibly affect the intra-epidermal nerve endings thus leading to the sensation of pruritus

Razlike u izražaju bjelančevina-regulatora apoptoze i proliferacije između zdrave kože i kože bolesnika s kroničnim bubrežnim zatajenjem i svrbežom

Svrbež je česta pojava u dijaliziranih bolesnika s kroničnim zatajenjem bubrega. U cilju istraživanja mogućih uzroka svrbeža u tih bolesnika, istraženo je 12 uzoraka kože uzete s bedra dijaliziranih bolesnika sa svrbežom i 5 uzoraka kože zdravih ispitanika. U histološkim rezovima navedenih uzoraka tkiva kože izmjerena je debljina epidermisa, a podatci su statistički obrađeni. Rezovi tkiva imunohistokemijski su obojani biljezima proliferacije Ki-67, antiapoptotskim biljegom Bcl-2, proapoptotskim biljezima Bax i kaspaza-3, a primijenjena je i TUNEL metoda za dokazivanje stanične smrti ili apoptoze. Naše je istraživanje pokazalo u kontrolnoj zdravoj koži proliferacijski indeks od 10.8 %, dok je u koži dijaliziranih bolesnika proliferacijski indeks bio 11.8 % nakon tri godine na dijalizi te 12.5 % nakon 5 godina dijalize. Navedeni rezultati ukazuju na povećani proliferacijski indeks u koži bolesnika na dijalizi te njegovu povezanost s trajanjem dijalize. Statistička analize mjesta stanične proliferacije u bazalnom i suprabazalnim slojevima, ukazala je da je u zdravih ispitanika proliferacija bila smještena ponajprije u bazalnom sloju dok je u dijaliziranih bolesnika uočen pad stanične proliferacije u bazalnom i suprabazalnom sloju nakon tri godine dijalize u odnosu na kožu zdravih ispitanika. Značajan pad proliferacije u suprabazalnim slojevima uočen je nakon pet godina dijalize u odnosu na kožu zdravih ispitanika kao i kožu dijaliziranih bolesnika nakon tri godine. Prosječna debljina epidermisa kože zdravih ispitanika iznosila je 53 μm, a u dijaliziranih bolesnika od 23 do 34 μm tijekom 3-5 godina trajanja dijalize. Ravnoteža između Bcl-2 i Bax bjelančevina nije se značajno promijenila u epidermisu dijaliziranih bolesnika nakon tri godine dijalize, u usporedbi s epidermisom kože zdravih ispitanika. Nakon petogodišnjeg razdoblja dijalize, uočen je pojačani izražaj proapoptotske Bax bjelančevine, a smanjeni izražaj antiapoptotske Bcl-2 bjelančevine u bazalnom i nazubljenom sloju epidermisa, kao i prisutnost apoptotskih stanica (TUNEL i kaspaza-3 pozitivnih) u površinskom i nazubljenom sloju epidermisa bolesnika sa svrbežom. Naše istraživanje dokazalo je prevladavanje proapoptotske Bax bjelančevine u odnosu na antiapoptotsku Bcl-2 bjelančevinu, kao i prisutnost apoptotskih stanica u dubljim slojevima epidermisa u bolesnika na dugotrajnoj dijalizi. Pretpostavljamo kako bi stanjenje epidermisa u tih bolesnika moglo biti povezano s pojavom apoptotskih stanica u dubljim epidermalnim slojevima, dok bi promjena unutarnje ravnoteže između stanica epidermisa mogla utjecati na živčane završetke smještene u epidermisu, s posljedičnim nastanka svrbeža.Chronic renal failure is often associated with skin itching (pruritus) in dialyzed patients. In order to investigate the possible causes of pruritus in those patients, the epidermis of the thigh of 12 dialyzed patients and 5 controls from patients without renal disease were examined. The sections of the epidermis were measured and statistically analyzed, and were immunohistochemically stained using antibodies to proliferation marker Ki-67, anti-apoptotic marker Bcl-2, and pro-apoptotic markers Bax and caspase-3, as well as TUNEL method. Proliferation index of epidermal cells was 10.8 % in normal skin, 11.3 % in the skin of patients after 3 years of dialysis and 12.5 % after 5 years of dialysis. An increased proliferation index characterized the skin of patients on dialysis, and accorded with duration of dialysis. After 3 years period on dialysis, a moderate increase of basal layer cell proliferation was noted in patient’s epidermis, while a significant decrease of proliferation in suprabasal layer of epidermis characterized patients after 5 years on dialysis. While the mean thickness of normal epidermis was 53 μm, in dialyzed patients it ranged between 23 and 34 μm during the 3–5 year period on dialysis. Compared to normal skin, the fine balance between the Bcl-2 and Bax proteins did not greatly change in the epidermis of dialyzed patients during the three years of dialysis. Following five-year dialysis, the epidermis displayed increased Bax and decreased Bcl-2 expression in the basal and intermediate epidermal layers, as well as the presence of apoptotic cells (TUNEL and caspase-3 positive) both in the superficial and intermediate epidermal layers. Our study demonstrated the predominant expression of cell death Bax proteins over cell survival Bcl-2 proteins, and apoptotic cells in the deeper layers of the epidermis in patients on long-term dialysis. We speculate that the thinning of the epidermis might be associated with the appearance of dead cells in the deeper epidermal layers, while the changed internal milieu of epidermal cells could possibly affect the intra-epidermal nerve endings thus leading to the sensation of pruritus

Razlike u izražaju bjelančevina-regulatora apoptoze i proliferacije između zdrave kože i kože bolesnika s kroničnim bubrežnim zatajenjem i svrbežom

Svrbež je česta pojava u dijaliziranih bolesnika s kroničnim zatajenjem bubrega. U cilju istraživanja mogućih uzroka svrbeža u tih bolesnika, istraženo je 12 uzoraka kože uzete s bedra dijaliziranih bolesnika sa svrbežom i 5 uzoraka kože zdravih ispitanika. U histološkim rezovima navedenih uzoraka tkiva kože izmjerena je debljina epidermisa, a podatci su statistički obrađeni. Rezovi tkiva imunohistokemijski su obojani biljezima proliferacije Ki-67, antiapoptotskim biljegom Bcl-2, proapoptotskim biljezima Bax i kaspaza-3, a primijenjena je i TUNEL metoda za dokazivanje stanične smrti ili apoptoze. Naše je istraživanje pokazalo u kontrolnoj zdravoj koži proliferacijski indeks od 10.8 %, dok je u koži dijaliziranih bolesnika proliferacijski indeks bio 11.8 % nakon tri godine na dijalizi te 12.5 % nakon 5 godina dijalize. Navedeni rezultati ukazuju na povećani proliferacijski indeks u koži bolesnika na dijalizi te njegovu povezanost s trajanjem dijalize. Statistička analize mjesta stanične proliferacije u bazalnom i suprabazalnim slojevima, ukazala je da je u zdravih ispitanika proliferacija bila smještena ponajprije u bazalnom sloju dok je u dijaliziranih bolesnika uočen pad stanične proliferacije u bazalnom i suprabazalnom sloju nakon tri godine dijalize u odnosu na kožu zdravih ispitanika. Značajan pad proliferacije u suprabazalnim slojevima uočen je nakon pet godina dijalize u odnosu na kožu zdravih ispitanika kao i kožu dijaliziranih bolesnika nakon tri godine. Prosječna debljina epidermisa kože zdravih ispitanika iznosila je 53 μm, a u dijaliziranih bolesnika od 23 do 34 μm tijekom 3-5 godina trajanja dijalize. Ravnoteža između Bcl-2 i Bax bjelančevina nije se značajno promijenila u epidermisu dijaliziranih bolesnika nakon tri godine dijalize, u usporedbi s epidermisom kože zdravih ispitanika. Nakon petogodišnjeg razdoblja dijalize, uočen je pojačani izražaj proapoptotske Bax bjelančevine, a smanjeni izražaj antiapoptotske Bcl-2 bjelančevine u bazalnom i nazubljenom sloju epidermisa, kao i prisutnost apoptotskih stanica (TUNEL i kaspaza-3 pozitivnih) u površinskom i nazubljenom sloju epidermisa bolesnika sa svrbežom. Naše istraživanje dokazalo je prevladavanje proapoptotske Bax bjelančevine u odnosu na antiapoptotsku Bcl-2 bjelančevinu, kao i prisutnost apoptotskih stanica u dubljim slojevima epidermisa u bolesnika na dugotrajnoj dijalizi. Pretpostavljamo kako bi stanjenje epidermisa u tih bolesnika moglo biti povezano s pojavom apoptotskih stanica u dubljim epidermalnim slojevima, dok bi promjena unutarnje ravnoteže između stanica epidermisa mogla utjecati na živčane završetke smještene u epidermisu, s posljedičnim nastanka svrbeža.Chronic renal failure is often associated with skin itching (pruritus) in dialyzed patients. In order to investigate the possible causes of pruritus in those patients, the epidermis of the thigh of 12 dialyzed patients and 5 controls from patients without renal disease were examined. The sections of the epidermis were measured and statistically analyzed, and were immunohistochemically stained using antibodies to proliferation marker Ki-67, anti-apoptotic marker Bcl-2, and pro-apoptotic markers Bax and caspase-3, as well as TUNEL method. Proliferation index of epidermal cells was 10.8 % in normal skin, 11.3 % in the skin of patients after 3 years of dialysis and 12.5 % after 5 years of dialysis. An increased proliferation index characterized the skin of patients on dialysis, and accorded with duration of dialysis. After 3 years period on dialysis, a moderate increase of basal layer cell proliferation was noted in patient’s epidermis, while a significant decrease of proliferation in suprabasal layer of epidermis characterized patients after 5 years on dialysis. While the mean thickness of normal epidermis was 53 μm, in dialyzed patients it ranged between 23 and 34 μm during the 3–5 year period on dialysis. Compared to normal skin, the fine balance between the Bcl-2 and Bax proteins did not greatly change in the epidermis of dialyzed patients during the three years of dialysis. Following five-year dialysis, the epidermis displayed increased Bax and decreased Bcl-2 expression in the basal and intermediate epidermal layers, as well as the presence of apoptotic cells (TUNEL and caspase-3 positive) both in the superficial and intermediate epidermal layers. Our study demonstrated the predominant expression of cell death Bax proteins over cell survival Bcl-2 proteins, and apoptotic cells in the deeper layers of the epidermis in patients on long-term dialysis. We speculate that the thinning of the epidermis might be associated with the appearance of dead cells in the deeper epidermal layers, while the changed internal milieu of epidermal cells could possibly affect the intra-epidermal nerve endings thus leading to the sensation of pruritus