Elevated leukocyte count as a harbinger of systemic inflammation, disease progression, and poor prognosis: a review.

Total leukocyte count increases significantly in response to infection, trauma, inflammation, and certain diseases. Factors affecting leukocyte count in healthy adults include sex, hormonal milieu, genetic inheritance, stress level, diet, nutrition, and lifestyle (e.g. tobacco-induced inflammatory changes, chronic psychological stress, etc.). To date, numerous studies have reported that high but normal leukocyte counts at baseline predict increased cardiovascular and noncardiovascular mortality in older adults. Recent findings suggest that elevated leukocyte count within the normal range, but especially neutrophil and monocyte counts, may be a harbinger of increased systemic inflammation and subclinical disease. Moreover, elderly people who tend to have high but normal leukocyte counts are at greater risk of cancer, cardiovascular disease, type 2 diabetes, some other age-related conditions, and they also have increased all-cause mortality. These results indicate that strong and reliable inflammatory markers, such as leukocyte count, may reflect the rate of ageing and therefore can predict long-term survival in the elderly. Remarkably, leukocyte count correlates positively with genuine markers of systemic inflammation like C-reactive protein and interleukin 6. Interestingly, some authors conclude that leukocyte counts have a stronger prognostic ability with regard to total and cardiovascular mortality than total cholesterol or low-density lipoproteins. The fact that these inflammatory markers are clinically useful predictors of long-term survival in the elderly is quite remarkable as these blood parameters are included in routine medical check-ups. Therefore, they can be used as simple and reliable morphological indicators of chronic systemic inflammation, disease progression, and poor prognosis, especially among individuals who are likely to develop age-related conditions. Nevertheless, the pathomechanism that links elevated but normal leukocyte counts to increased mortality remains poorly understood. This review summarises the most important findings on the links between leukocyte count, chronic systemic inflammation, and health outcomes in older adults. (Folia Morphol 2018; 77, 2: 171-178).

The Terminologia Anatomica matters: examples from didactic, scientific, and clinical practice.

The proper usage of the anatomical terminology is of paramount importance to all medical professionals. Although a multitude of studies have been devoted to issues associated with the use and application of the recent version of the anatomical terminology in both theoretical medicine and clinical practice, there are still many unresolved problems such as confusing terms, inconsistencies, and errors, including grammar and spelling mistakes. The aim of this article is to describe the current situation of the anatomical terminology and its usage in practice, as well as explain why it is so important to use precise, appropriate, and valid anatomical terms during the everyday communication among physicians from all medical branches. In this review, we discuss some confusing, obsolete, and erroneous terms that are still commonly used by many clinicians, and surgeons in particular, during the process of diagnosis and treatment. The use of these ambiguous, erroneous, and obsolete terms enhances the risk of miscommunication. We also provide some edifying examples from everyday clinical practice.

Next-generation sequencing for diagnosis of thoracic aortic aneurysms and dissections: diagnostic yield, novel mutations and genotype phenotype correlations.

BACKGROUND: Thoracic aortic aneurysms and dissections (TAAD) are silent but possibly lethal condition with up to 40 % of cases being hereditary. Genetic background is heterogeneous. Recently next-generation sequencing enabled efficient and cost-effective examination of gene panels. Aim of the study was to define the diagnostic yield of NGS in the 51 TAAD patients and to look for genotype-phenotype correlations within families of the patients with TAAD. METHODS: 51 unrelated TAAD patients were examined by either whole exome sequencing or TruSight One sequencing panel. We analyzed rare variants in 10 established thoracic aortic aneurysms-associated genes. Whenever possible, we looked for co-segregation in the families. Kaplan-Meier survival curve was constructed to compare the event-free survival depending on genotype. Aortic events were defined as acute aortic dissection or first planned aortic surgery. RESULTS AND DISCUSSION: In 21 TAAD patients we found 22 rare variants, 6 (27.3 %) of these were previously reported, and 16 (73.7 %) were novel. Based on segregation data, functional analysis and software estimations we assumed that three of novel variants were causative, nine likely causative. Remaining four were classified as of unknown significance (2) and likely benign (2). In all, 9 (17.6 %) of 51 probands had a positive result when considering variants classified as causative only and 18 (35.3 %) if likely causative were also included. Genotype-positive probands (n = 18) showed shorter mean event free survival (41 years, CI 35-46) than reference group, i.e. those (n = 29) without any plausible variant identified (51 years, CI 45-57, p = 0.0083). This effect was also found when the 'genotype-positive' group was restricted to probands with 'likely causative' variants (p = 0.0092) which further supports pathogenicity of these variants. The mean event free survival was particularly low (37 years, CI 27-47) among the probands with defects in the TGF beta signaling (p = 0.0033 vs. the reference group). CONCLUSIONS: This study broadens the spectrum of genetic background of thoracic aneurysms and dissections and supports its potential role as a prognostic factor in the patients with the disease.

Typology of the antegonial notch in the human mandible.

BACKGROUND: Surgical treatment for serious malocclusions and fractures of the organ of mastication is a golden standard in medicine. Procedures performed on the mandible require detailed knowledge of the anatomy of the organ. Antegonial notching constitutes a serious technical challenge for surgeons. Therefore, a detailed anatomical description of this structure, which is the subject of this paper, is essential. MATERIALS AND METHODS: We analysed 251 human Caucasian mandibles of identified sex and took measurements of all sections describing the mandibular antegonial notch. Depending on the proportion between sections we classified the shape of the antegonial notch into three types. The surface area of the notch was calculated. We analysed the dimorphic and bilateral differences for each of the three types of notch. We used variance analysis for the assessment of statistical difference. RESULTS: The analysis revealed that in both men and women, regardless of body side, the type 3 antegonial notch was the most frequent. Type 3 occurred with a frequency of between 38% in men on the right side and 55.9% in women on the left side of the body. Type 1 was the least frequent. Dimorphic differences in the presence of individual types of antegonial notch were statistically significant only for the left side of the body. The symmetrical type (type 2) occurred more frequently in men (by 11%) than in women. Type 3 was found more frequently in women (by 10%) than in men. Bilateral differences in men were revealed for the frequencies of types 1 and 3. On the right side type 1 was more frequent (by 8%), and on the left side type 3 was also more frequent (by 8%). The greatest surface area was found for the asymmetrical posterior type (type 1). The smallest surface area was found for the asymmetrical anterior type 3. This difference was statistically significant with respect to the surface area of types 1 and type 2 and found for both sexes for both sides of the body. However, no statistically significant differences were found between the surface areas of types 1 or 2. CONCLUSIONS: Knowledge of the preangular notch anatomy can be useful for surgeons during reconstructive and plastic procedures on the body of the mandible.

Vascular architecture of the human uterine cervix, as assessed in light- and scanning electron microscopy.

BACKGROUND: The aim of this study was to visualise and describe the vasculature of the human uterine cervix. MATERIAL AND METHODS: The material for this study was obtained from women (age between 20 to 45 years) during autopsy. The material was collected not later than 24 h post-mortem. This study was performed using uteri from cadavers of menstruating nulliparas (33 uteri) and menstruating multiparas (27 uteri). Collected uteri were perfused via the afferent vessels with Mercox resin (for corrosion-casting and SEM assessment) or acrylic paint solution (light microscopy assessment). The research protocol was approved by the Jagiellonian University Ethics Committee (registry KBET/121/8/2007). RESULTS: In all cases bilateral cervical branches (1-4), originating from the uterine artery, were found. Both in the vaginal and supravaginal parts of the cervix, four distinct vascular zones were found. In the pericanalar zone ran small veins, responsible for draining the mucosal capillaries. Both in the muscular layer, as well as in the pericanalar zone, arterioles, and venules passed close to each other, often adjoining. CONCLUSIONS: This study does not confirm the existence of a single cervicovaginal artery, but shows that the vascular supply of the cervix comes from several vessels. It also introduces the idea of two systems, responsible for draining blood from the mucosal capillaries. Neither assessment in light microscopy nor in SEM revealed any differences between multiparas and nulliparas, regarding the vascular architecture of the cervix.

New Terminologia Anatomica highlights the importance of clinical anatomy.

Although not all authors agree that Terminologia Anatomica merits special attention, any type of scientific terminology should be clear, exact, logical, coherent and worldwide accepted. A precise definition of every anatomical term is also crucial. New changes have recently been approved by the Federative International Programme for Anatomical Terminology as the previous version of terminology required minor revisions. This situation offers an opportunity to take a closer look at these new and interesting modifications. It turns out that selected traditional terms have been excluded from the list of official anatomical names. Furthermore, many changes have been introduced to modernise the Terminologia Anatomica. Nevertheless, the new version of anatomical terminology has both strengths and limitations, which warrants further refinement.

Should Terminologia Anatomica be revised and extended? A critical literature review.

The first edition of the Terminologia Anatomica was published in 1998 by the Federative Committee for Anatomical Terminology, whereas the second edition was issued in 2011 by the Federative International Programme for Anatomical Terminologies. Since then many attempts have been made to revise and extend the official terminology as several inconsistencies have been noted. Moreover, numerous crucial terms were either omitted or deliberately excluded from the official terminology, like sulcus popliteus and diaphragma urogenitale, respectively. Furthermore, several synonyms are to be discarded. Notwithstanding the criticism, the use of the current version of terminology is strongly recommended. Although the Terminologia Anatomica is open to future expansion and revision, every change should be made after a thorough discussion of the historical context and scientific legitimacy of a given term. The anatomical nomenclature must be as simple as possible but also precise and coherent. It is generally accepted that hasty innovation ought not to be endorsed. Therefore, there is a need to take a closer look at these new proposals as they have been presented in numerous dispersed papers. This article provides an overview of these issues and concentrates on selected revisions and extensions that are didactically and clinically useful, thereby summarising the salient aspects of these new and compelling proposals.

Terminologia Anatomica and its practical usage: pitfalls and how to avoid them.

In 2016, the Federative International Programme for Anatomical Terminology tentatively approved the updated and extended version of anatomical terminology that replaced the previous version of Terminologia Anatomica (1998). This modern version has already appeared in new editions of leading anatomical atlases and textbooks, including Netter's Atlas of Human Anatomy, even though it was originally available only as a draft and the final version is different. We believe that updated and extended versions of anatomical terminology are important and they can be a powerful tool in communication between anatomists and other specialists around the world. In general, the new version uses more precise and adequate anatomical terms and many segments, including the part dealing with the nervous system, which is also known as the Terminologia Neuroanatomica, have been considerably improved. Nevertheless, some segments have not been extended or modernised, while other parts have been modified considerably, thereby posing a challenge to those who prefer the traditional version of Latin terminology because a number of official names for bones, muscles, organs and blood vessels have been changed. Whilst most of these changes seem to be inspired by a long anatomical tradition and thus cannot come as a surprise to anyone in the field, other modifications are characterised by terminological innovativeness. Selected new and unexpected changes that might cause confusion among those who prefer traditional anatomical terms and definitions are discussed here.

Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: sequential triple biopsy studies with micro-computed tomography.

The objective of the study was to assess the time course of changes in bone mineralization and architecture using sequential triple biopsies from women with postmenopausal osteoporosis (PMO) who received long-term treatment with risedronate. Transiliac biopsies were obtained from the same subjects (n = 7) at baseline and after 3 and 5 years of treatment with 5 mg daily risedronate. Mineralization was measured using 3-dimensional (3D) micro-computed tomography (CT) with synchrotron radiation and was compared to levels in healthy premenopausal women (n = 12). Compared to the untreated PMO women at baseline, the premenopausal women had higher average mineralization (Avg-MIN) and peak mineralization (Peak-MIN) by 5.8% (P = 0.003) and 8.0% (P = 0.003), respectively, and lower ratio of low to high-mineralized bone volume (BMR-V) and surface area (BMR-S) by 73.3% (P = 0.005) and 61.7% (P = 0.003), respectively. Relative to baseline, 3 years of risedronate treatment significantly increased Avg-MIN (4.9 +/- 1.1%, P = 0.016) and Peak-MIN (6.2 +/- 1.5%, P = 0.016), and significantly decreased BMR-V (-68.4 +/- 7.3%, P = 0.016) and BMR-S (-50.2 +/- 5.7%, P = 0.016) in the PMO women. The changes were maintained at the same level when treatment was continued up to 5 years. These results are consistent with the significant reduction of turnover observed after 3 years of treatment and which was similarly maintained through 5 years of treatment. Risedronate restored the degree of mineralization and the ratios of low- to high-mineralized bone to premenopausal levels after 3 years of treatment, suggesting that treatment reduced bone turnover in PMO women to healthy premenopausal levels. Conventional micro-CT analysis further demonstrated that bone volume (BV/TV) and trabecular architecture did not change from baseline up to 5 years of treatment, suggesting that risedronate provided long-term preservation of trabecular architecture in the PMO women. Overall, risedronate provided sustained benefits on mineralization and architecture, two key determinants of bone strength, over 5 years lending support for its long-term efficacy in fracture risk reduction.

Simvastatin did not prevent nor restore ovariectomy-induced bone loss in adult rats.

Current published results on whether statins have beneficial effects on bone metabolism have been conflicting so far. In order to further investigate if statins were promising candidates for the treatment for osteoporosis, we conducted a study in which rats were ovariectomized (OVX) at 6 months of age, allowed to lose bone for 60 days and followed by oral administration of simvastatin at the dose levels of 0.3-10 mg/kg/d for 60 days. PGE2 (6 mg/kg) was used as a positive control. Study endpoints included bone histomorphometry on the proximal tibial metaphysis (PTM) and the tibial diaphysis (TX), dual-energy X-ray absorptiometry on the right femur and micro computed tomography (ICT) on the 5th lumbar vertebra (LV). After 120 days of OVX, cancellous bone lost by 80% in the PTM and 18% in the LV accompanied by increased bone formation and resorption. Simvastatin at all dose levels did not affect bone volume, bone formation rate and bone erosion surface when compared to 120 day ovariectomized animals at all bone sites studied. By contrast, PGE2 restored cancellous and cortical bone area to sham control levels. In conclusion, this study demonstrated that unlike PGE2, oral administration of simvastatin did not have effects on cancellous or cortical bone formation and resorption; and consequently was not able to prevent further bone loss or restore bone mass in the osteopenic, OVX rats.

New potent sensitizers for photodynamic therapy: 21-oxaporphyrin, 21-thiaporphyrin and 21,23-dithiaporphyrin induce extensive tumor necrosis.

New sensitizers for photodynamic therapy (PDT) are reported. These compounds, namely 21-thiaporphyrin, 21,23-dithiaporphyrin and 21-oxaporphyrin, reveal some of the properties required for such therapy. Their physicochemical, chemical and pharmacological features meant that we could use them in the treatment of transplantable BFS1 fibrosarcoma in Balb/c mice. New sensitizers and the well-known chlorin e6 (Ce6) were used in doses of 2.5, 5.0, 7.5 and 10.0 mg/kg body weight, given intraperitoneally and followed by light irradiation, the total light doses being 50, 100 and 150 J/cm(2) within 24 h after injection. The effectiveness of new sensitizers in PDT was evaluated with in terms of tumor necrosis intensity, the survival time of treated animals, the rate of tumor response (complete/partial/no response), and skin photosensitivity. These results were compared to results obtained in analogous conditions after Ce6-PDT. Distribution studies revealed that the highest concentration of new compounds occurred within 24 h after injection. The results of these experiments confirmed that 21-thiaporphyrin, 21,23-dithiaporphyrin and 21-oxaporphyrin can be considered as potent tumor photosensitizers that do not exert any unwanted effects, primarily skin photosensitization. We suggest that these porphyrins are possible sensitizers to be applied in clinical PDT.

Interactions between the effects of basal forebrain lesions and chronic treatment with MDL 26,479 on learning and markers of cholinergic transmission.

The effects of ibotenic acid-induced basal forebrain lesions and treatment with the triazole MDL 26,479 on the acquisition of an operant visual conditional discrimination task and on [3H]hemicholinium-3 and [3H]vesamicol binding were examined. Lesioned animals required more training sessions to acquire the stimulus-response rules of this task. They also showed longer response latencies throughout the experiment. The effects of the treatment with MDL 26,479 (5 mg/kg; i.p. 60 min before each training session) interacted with the effects of the lesion, producing a decrease in the number of sessions required to perform above chance-level in lesioned but not in control animals. MDL 26,479 did not seem to produce immediate performance effects but interacted with the learning process. The lesions destroyed the cell bodies in the area of the substantia innominata, basal nucleus of Meynert, and the globus pallidus. The number of frontocortical cholinergic terminals as primarily indicated by hemicholinium-3 binding was reduced in lesioned animals; however, another measure of cholinergic terminals, vesamicol binding, was unchanged. Behavioral performance of animals correlated significantly with hemicholinium binding in the frontal cortex of the right hemisphere. The fact that the lesion delayed but did not block the acquisition of the task may have been a result of compensatory mechanisms in remaining cholinergic terminals as indicated by stable vesamicol binding. These data allow assumptions about the conditions for the demonstration of beneficial behavioral effects of MDL 26,479. They also suggest that the long-term effects of basal forebrain lesions on cortical cholinergic transmission remain unsettled.

Temporal dependent neuroprotection with propentofylline (HWA 285) in a temporary focal ischemia model.

Propentofylline (HWA 285, 3-methyl-1-(5-oxo-hexyl)-7-propylxanthine) is an adenosine uptake and phosphodiesterase inhibitor that has been shown to be neuroprotective in both global and permanent focal ischemia animal models. However, to date, the efficacy of propentofylline has never been examined in an animal model of temporary focal ischemia or the 'therapeutic window' systematically examined in a focal ischemia model. The present experiments were designed to investigate these. Temporary (3 h) middle cerebral artery occlusion was accomplished by the monofilament method. Infarct volumes were determined at 24 h from 2,3,5-triphenyltetrazolieum chloride (TTC) stained coronal slices. Animals were dosed with vehicle or propentofylline at 3 mg/kg bolus and/or a 6 mg/kg per h infusion (24 h infusion) at 30 min, 1 h or 3 h post ischemia onset. Physiological monitoring on a subset of animals indicated no changes in mean arterial pressure, blood gases, blood pH, and glucose levels with either ischemia or drug treatment. Propentofylline treatment resulted in a statistically significant decrease in infarct volume when an infusion dose of 6 mg/kg per h was initiated at 30 min or when a bolus of 3 mg/kg plus an infusion dose was initiated at 1 h but not 3 h post ischemia. Therefore, propentofylline is neuroprotective in a model of temporary focal ischemia. This suggests that combination therapy with propentofylline might lead to clinical improvement beyond that which would occur with thrombolytics alone. The apparent short window of opportunity for effective dosing is consistent with the proposed mechanism of action for propentofylline.

The regulation of high-affinity choline uptake in vitro in rat cortical and hippocampal synaptosomes by beta-carbolines administered in vivo.

The effects of several beta-carboline derivatives on sodium-dependent high-affinity choline uptake (HACU) were investigated in rat hippocampus and cerebral cortex. HACU was measured in synaptosomal preparations from these areas after in vivo administration of the drugs. The convulsant, picrotoxin (6 mg/kg), stimulated HACU in both hippocampal and cortical synaptosomes. The convulsant inverse agonist benzodiazepine, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) (5 mg/kg) stimulated hippocampal but not cortical HACU. However, other inverse agonists, methyl-beta-carboline-3-carboxylate (beta-CCM) (20 mg/kg) and ethyl-beta-carboline-3-carboxylate (beta-CCE) (20 mg/kg), stimulated HACU in the cortex but not in the hippocampus. The partial inverse agonist, N-methyl-beta-carboline-3-carboxylate (FG-7142) (20 mg/kg), inhibited cortical HACU and had no effect on hippocampal HACU. The antagonist beta-carboline, 3-hydroxymethyl-beta-carboline (3-HMC) (20 mg/kg), had no effect on either cortical or hippocampal HACU. None of these drugs displayed any effect on HACU when they were incubated directly in vitro with synaptosomal preparations at concentrations up to 100 microM, suggesting their activity is not directly on the cholinergic nerve terminal. The results suggest that beta-carbolines regulate hippocampal and cortical cholinergic activity as do other GABAergic drugs. However, unlike diazepam, which depresses cholinergic activity in both the hippocampus and the cortex the beta-carbolines differentiate between the hippocampus and cortex in their action.

The enhancement of muscimol-stimulated 36C1 influx by the antispastic 5-aryl-3-(alkylsulfonyl)-4H-1,2,4-triazole (MDL 27,531) in rat brain membrane vesicles.

The antispastic triazole, 4-methyl-3-methylsulphonyl-5-phenyl-4H-1,2,4-triazole (MDL 27,531) was tested in glycine- and muscimol-stimulated 36Cl- influx into brain membrane preparations. MDL 27,531 (100 nM) had no effect on glycine- (100 nM-400 microM) stimulated 36Cl- influx in brain stem tissue; on the other hand, MDL 27,531 (10 nM-10 microM) enhanced muscimol- (1 microM) stimulated 36Cl- influx in cerebellar but not cortical membranes. In the presence of the benzodiazepine (BZD) antagonist, flumazenil (10 microM), MDL 27,531 inhibited muscimol-stimulated flux. These data suggest a novel interaction of this triazole with subtypes of the gamma-aminobutyric acid (GABA)A receptor complex and the BZD receptor.

Ethnicity and gender in scales of psychosis proneness and mood disorders.

Data for Caucasian, African American, Asian American, and Latino college-student samples were compared for several popular self-report scales of psychopathology. Significant group differences were obtained for all scales, with the Caucasian sample consistently having the lowest means. Some gender effects and interactions with ethnic group were also observed. The authors discuss implications of these findings for use of these scales, including implications for use of Caucasian norms with other ethnic samples.

MDL 101,002, a free radical spin trap, is efficacious in permanent and transient focal ischemia models.

The present work describes the neuroprotective effects of the free radical spin trap, MDL 101,002, in models of permanent and transient focal ischemia. Permanent focal ischemia was carried out by occlusion of the distal segment of the middle cerebral artery (MCA) and CCA's in Spontaneously Hypertensive (SH) and Wistar rats. Transient focal ischemia was undertaken by occluding the origin of the MCA for 180 min by the intraluminar monofilament method in Wistar rats. With permanent distal MCA occlusion in SH rats, 100 mg/kg i.v. at 30 min post-ischemia resulted in a significant 40% reduction in infarct volume. Similarly, a 75 mg/kg bolus + 45 mg/kg-h dose of MDL 101,002 given i.v. at 5 min post-ischemia resulted in a 90% or 60% decrease in infarct volume in the mixed permanent/transient distal MCA model with Wistar rats using 120 or 180 min of CCA occlusion, respectively. When full reperfusion was established, after 180 min of occlusion in the proximal MCA model, a dose of 40 mg/kg + infusion and 75 mg/kg + infusion resulted in a significant 50% and 70% decrease in ischemic damage, respectively. MDL 101,002 is clearly an effective neuroprotective agent in all models examined. This work would suggest that this novel cyclic nitrone spin trap affords effective neuroprotection and is useful for the treatment of ischemic stroke.

The new sensitizing agents for photodynamic therapy: 21-selenaporphyrin and 21-thiaporphyrin.

BACKGROUND: Photodynamic therapy may be a promising treatment for patients with tumors. The mechanism of its action is poorly understood and different from the cytotoxic effects induced by antitumor drugs. MATERIALS AND METHODS: New sensitizers, termed as 21-selenaporphyrin (SEP) and 21-thiaporphyrin (STSP) were studied for their photocytotoxicity in vitro against selected human cancer cell lines. This study was followed by in vivo screening of the effect of SEP using an animal tumor model. The activity of the new agents was compared with that of a known photosensitizer, namely chlorin e6. In our selection of the cell lines applied for in vitro study, the possible accessibility and effectiveness of photodynamic therapy (PDT) for treatment of colon and urinary bladder cancers, was considered. RESULTS: New compounds appeared to be not toxic for tested cells in culture, without exposure to light. The STSP exerted in vitro effects comparable with chlorin e6 photocytotoxicity, while SEP appeared to be ineffective. However, in vivo experiments performed in a BFS1 fibrosarcoma tumor model in mice showed that the SEP was at least as much effective as chlorin e6 in the induction of tumor necrosis. In contrast to chlorin e6, SEP-PDT induced no skin sensitization. CONCLUSIONS: Both new sensitizers can be applied in PDT at no risk of skin damage. The mechanism of the action of these two compounds is probably different, i.e. the 21-thiaporphyrin possibly acts directly on tumor cells and the 21-selenaporphyrin via endothelial cells of newly formed tumor vasculature.

Tumor histopathology following new sensitizers: dithiaporphyrin- and sulfoxaporphyrin-mediated photodynamic therapy.

BACKGROUND: Our main aim was to evaluate tumor histopathology following new sensitizer-mediated photodynamic therapy (PDT). MATERIALS AND METHODS: In order to complete our studies we decided to use photosensitizers, i.e. dithiaporphyrin (DTP) and sulfoxaporphyrin (OXA) in combination with halogen lamp irradiation of presensitized tumors. The doses of sensitizers were: 2.5, 5.0, 7.5 and 10.0 mg/kg of body weight and total light doses were: 50, 100 and 150 J/sq.cm at the selected wavelength. Following such a treatment we have evaluated tumor necrosis of BFS1 fibrosarcoma growing on BALB/c mice. Together with tumor necrosis evaluation we have examined skin response to photodynamic treatment. RESULTS: We have found that both new sensitizers caused significant tumor damage at no skin alterations. The induction of tumor necrosis seemed to be dose dependent, i.e. higher photodynamic doses (sensitizer dose x light dose) resulted in more severe damage to the tumors than the lower doses. CONCLUSION: Our study showed that BFS1 fibrosarcoma is highly sensitive to PDT after application of new sensitizers. Both compounds can be considered as potent tumor photosensitizers in future clinical trials.

5,20-bis(4-sulphophenyl)-10,15-bis (2-methoxy-4-sulphophenyl)-21-thiaporphyrin as a new potent sensitizer in photodynamic therapy.

The main purpose of the study was to investigate the effectiveness of a new photosensitizer for photodynamic therapy. 5,20-bis(4-sulphophenyl)-10,15-bis (2-methoxy-4-sulphophenyl)-21-thiaporphyrin (21-thiaporphyrin) was compared to chlorin e6 and tetra(m-hydroxyphenyl)porphyrin (m-THPP) for its ability to sensitize tumors and skin to light. Chlorin e6 and m-THPP induced a strong tumor and skin photosensitization. In contrast, the same doses of 21-thiaporphyrin produced no skin sensitization and gave approximately 10 mm tumor necrosis after light exposure, in comparison to the 5-6 mm necrosis induced by chlorin e6 or m-THPP under identical conditions. 21-Thiaporphyrin, tested as a potential photosensitizer, induced no skin sensitization even at doses as high as 7.5 mg/kg body weight. 21-Thiaporphyrin presents a high potency in tumor sensitizing, i.e. a feature required for an efficient photosensitizer in photodynamic therapy applications.