Biogenic Iron Preserves Structures during Fossilization: A Hypothesis: Iron from Decaying Tissues May Stabilize Their Morphology in the Fossil Record.

It is hypothesized that iron from biological tissues, liberated during decay, may have played a role in inhibiting loss of anatomical information during fossilization of extinct organisms. Most tissues in the animal kingdom contain iron in different forms. A widely distributed iron-bearing molecule is ferritin, a globular protein that contains iron crystallites in the form of ferrihydrite minerals. Iron concentrations in ferritin are high and ferrihydrites are extremely reactive. When ancient animals are decaying on the sea floor under anoxic environmental conditions, ferrihydrites may initialize the selective replication of some tissues in pyrite FeS2 . This model explains why some labile tissues are preserved, while other more resistant structures decay and are absent in many fossils. A major implication of this hypothesis is that structures described as brains in Cambrian arthropods are not fossilization artifacts, but are instead a source of information on anatomical evolution at the dawn of complex animal life.

Steps towards establishing a new medical college in the Kingdom of Saudi Arabia: an insight into medical education in the Kingdom.

BACKGROUND: The percentage of Saudi physicians practicing in the public health sector did not exceed 22.6% in 2009, and did not reach 20% in 2006. This is despite the fact that more than 80% of the Saudi population seeks health care in the public health sector. Such a low percentage of Saudi physicians is even significantly lower in the private health sector. With a fast growing population, and a low percentage of Saudi nationals practicing medicine, the need to establish new medical colleges in the Kingdom became a must. This study reflects on the steps followed in establishing the College of Medicine at Al-Imam Mohammad Ibn Saud Islamic University, and provides a comprehensive insight into medical education in the Kingdom. METHODS: A sub-committee derived from the Saudi Medical Colleges Deans' Committee was created and chaired by the founding dean of Al-Imam College of Medicine. The main goals of the sub-committee were to analyze the status of medical education in the Kingdom, and to produce an action plan to be followed when establishing a new medical college in the country. RESULTS: The sub-committee produced a working document, which included recommendations and action plan. A medical college yet to be established should take into consideration right from the beginning both institutional and program accreditation. To achieve this goal, there are five main pillars to be planned by six main task forces. Embedded among these pillars are twenty-one domains. The analysis of the status of medical education in the Kingdom revealed some interesting observations, which are discussed in details in the manuscript. CONCLUSIONS: Establishing a new medical college should not be about just increasing the number of medical colleges as a response to the shortage of doctors. It is a lengthy "surgical operation" that requires careful and timely planning in order to anticipate and prevent any damage, and to ensure optimal outcomes. In this regard, a detailed analysis of what already exists and what needs to be done is crucial.

Analysis of the effect of the active compound of green tea (EGCG) on the proliferation of peripheral blood mononuclear cells.

BACKGROUND: Cancer immunotherapy requires proper manipulation of the immune system, lymphocytes in particular, in order to identify and destroy the cancer cells as non-self. In this study we investigated the effect of the flavonoid present in green tea, namely epigallocatechin-3-gallate (EGCG), on the proliferation of, and IFN-γ production by, peripheral blood mononuclear cells (PBMC) from breast cancer patients stimulated with a mitogen, anti-CD3 and the common breast cancer peptides Her-2/neu, and p53. METHODS: Blood samples were collected from 25 patients with breast cancer at the Kuwait Cancer Control Centre (KCCC). The patients were newly diagnosed, and had not undergone any treatment or surgery at the time of sample collection. The control group consisted of 25 healthy women age-matched (±5 years) to the patients. PBMC were isolated from the patients and controls, and were cultured separately with the mitogen PHA, anti-CD3 antibodies, and Her-2/neu and p53 in the presence or absence of standardized doses of EGCG. The degree of proliferation and interferon-γ [IFN-γ) release were then analyzed. RESULTS: EGCG significantly suppressed the proliferation of PBMC in response to stimulation separately with (i) the mitogen, (ii) anti-CD3, and (iii) the cancer antigen peptides. IFN-γ production was also significantly suppressed by EGCG in vitro. CONCLUSIONS: EGCG appears to have an immunosuppressive effect on the proliferation of PBMC, indicating that EGCG is worth exploring for immunomodulatory effects in autoimmune diseases and tissue transplantation.

The effects of clays on bacterial community composition during arthropod decay.

Fossilization, or the transition of an organism from the biosphere to the geosphere, is a complex mechanism involving numerous biological and geological variables. Bacteria are one of the most significant biotic players to decompose organic matter in natural environments, early on during fossilization. However, bacterial processes are difficult to characterize as many different abiotic conditions can influence bacterial efficiency in degrading tissues. One potentially important variable is the composition and nature of the sediment on which a carcass is deposited after death. We experimentally examined this by decaying the marine shrimp Palaemon varians underwater on three different clay sediments. Samples were then analyzed using 16S ribosomal RNA sequencing to identify the bacterial communities associated with each clay system. Results show that samples decaying on the surface of kaolinite have a lower bacterial diversity than those decaying on the surface of bentonite and montmorillonite, which could explain the limited decay of carcasses deposited on this clay. However, this is not the only role played by kaolinite, as a greater proportion of gram-negative over gram-positive bacteria is observed in this system. Gram-positive bacteria are generally thought to be more efficient at recycling complex polysaccharides such as those forming the body walls of arthropods. This is the first experimental evidence of sediments shaping an entire bacterial community. Such interaction between sediments and bacteria might have contributed to arthropods' exquisite preservation and prevalence in kaolinite-rich Lagerstätten of the Cambrian Explosion. Supplementary Information: The online version contains supplementary material available at 10.1186/s13358-024-00324-7.

The Cabrières Biota (France) provides insights into Ordovician polar ecosystems.

Early Palaeozoic sites with soft-tissue preservation are predominantly found in Cambrian rocks and tend to capture past tropical and temperate ecosystems. In this study, we describe the diversity and preservation of the Cabrières Biota, a newly discovered Early Ordovician Lagerstätte from Montagne Noire, southern France. The Cabrières Biota showcases a diverse polar assemblage of both biomineralized and soft-bodied organisms predominantly preserved in iron oxides. Echinoderms are extremely scarce, while sponges and algae are abundantly represented. Non-biomineralized arthropod fragments are also preserved, along with faunal elements reminiscent of Cambrian Burgess Shale-type ecosystems, such as armoured lobopodians. The taxonomic diversity observed in the Cabrières Biota mixes Early Ordovician Lagerstätten taxa with Cambrian forms. By potentially being the closest Lagerstätte to the South Pole, the Cabrières Biota probably served as a biotic refuge amid the high-water temperatures of the Early Ordovician, and shows comparable ecological structuring to modern polar communities.

Variations in preservation of exceptional fossils within concretions.

Concretions are an interesting mode of preservation that can occasionally yield fossils with soft tissues. To properly interpret these fossils, an understanding of their fossilization is required. Probabilistic models are useful tools to identify variations between different Konservat-Lagerstätten that are separated spatially and temporally. However, the application of probabilistic modeling has been limited to Early Paleozoic Konservat-Lagerstätten preserved in shales. In this paper, the patterns of preservation of three concretionary Konservat-Lagerstätten-the Carboniferous Mazon Creek (USA) and Montceau-les-Mines (France), and the Silurian Herefordshire Lagerstätte (UK)-are analyzed using a statistical approach. It is demonstrated that the degree of biotic involvement, i.e., the degree to which a carcass dictates its own preservation, is connected to internal organ conditional probabilities-the probabilities of finding an internal organ associated with another structure such as biomineralized, sclerotized, cuticularized, or cellular body walls. In concretions that are externally forced with little biological mediation (e.g., Herefordshire), all internal organ conditional probabilities are uniform. As biological mediation in concretion formation becomes more pronounced, heterogeneities in conditional probabilities are introduced (e.g., Montceau-les-Mines and Mazon Creek). The three concretionary sites were also compared with previously investigated Konservat-Lagerstätten preserving fossils in shales to demonstrate how the developed probability framework aids in understanding the broad-scale functioning of preservation in Konservat-Lagerstätten. Supplementary Information: The online version contains supplementary material available at 10.1186/s13358-023-00284-4.

Young coconut juice can accelerate the healing process of cutaneous wounds.

BACKGROUND: Estrogen has been reported to accelerate cutaneous wound healing. This research studies the effect of young coconut juice (YCJ), presumably containing estrogen-like substances, on cutaneous wound healing in ovairectomized rats. METHODS: Four groups of female rats (6 in each group) were included in this study. These included sham-operated, ovariectomized (ovx), ovx receiving estradiol benzoate (EB) injections intraperitoneally, and ovx receiving YCJ orally. Two equidistant 1-cm full-thickness skin incisional wounds were made two weeks after ovariectomy. The rats were sacrificed at the end of the third and the fourth week of the study, and their serum estradiol (E2) level was measured by chemiluminescent immunoassay. The skin was excised and examined in histological sections stained with H&E, and immunostained using anti-estrogen receptor (ER-α an ER-ß) antibodies. RESULTS: Wound healing was accelerated in ovx rats receiving YCJ, as compared to controls. This was associated with significantly higher density of immunostaining for ER-α an ER-ß in keratinocytes, fibroblasts, white blood cells, fat cells, sebaceous gland, skeletal muscles, and hair shafts and follicles. This was also associated with thicker epidermis and dermis, but with thinner hypodermis. In addition, the number and size of immunoreactive hair follicles for both ER-α and ER-ß were the highest in the ovx+YCJ group, as compared to the ovx+EB group. CONCLUSIONS: This study demonstrates that YCJ has estrogen-like characteristics, which in turn seem to have beneficial effects on cutaneous wound healing.

Probability-based preservational variations within the early Cambrian Chengjiang biota (China).

The Chengjiang biota (Yunnan Province, China) is a treasure trove of soft-bodied animal fossils from the earliest stages of the Cambrian explosion. The mechanisms contributing to its unique preservation, known as the Burgess Shale-type preservation, are well understood. However, little is known about the preservation differences between various animal groups within this biota. This study compares tissue-occurrence data of 11 major animal groups in the Chengjiang biota using a probabilistic methodology. The fossil-based data from this study is compared to previous decay experiments. This shows that all groups are not equally preserved with some higher taxa more likely to preserve soft tissues than others. These differences in fossil preservation between taxa can be explained by the interaction of biological and environmental characteristics. A bias also results from differential taxonomic recognition, as some taxa are easily recognized from even poorly preserved fragments while other specimens are difficult to assign to higher taxa even with exquisite preservation.

New fossil assemblages from the Early Ordovician Fezouata Biota.

The Fezouata Biota (Morocco) is a unique Early Ordovician fossil assemblage. The discovery of this biota revolutionized our understanding of Earth's early animal diversifications-the Cambrian Explosion and the Ordovician Radiation-by suggesting an evolutionary continuum between both events. Herein, we describe Taichoute, a new fossil locality from the Fezouata Shale. This locality extends the temporal distribution of fossil preservation from this formation into the upper Floian, while also expanding the range of depositional environments to more distal parts of the shelf. In Taichoute, most animals were transported by density flows, unlike the in-situ preservation of animals recovered in previously investigated Fezouata sites. Taichoute is dominated by three-dimensionally preserved, and heavily sclerotized fragments of large euarthropods-possibly representing nektobenthic/nektic bivalved taxa and/or hurdiid radiodonts. Resolving whether this dominance reflects a legitimate aspect of the original ecosystem or a preservational bias requires an in-depth assessment of the environmental conditions at this site. Nevertheless, Taichoute provides novel preservational and palaeontological insights during a key evolutionary transition in the history of life on Earth.

The Chengjiang Biota inhabited a deltaic environment.

The Chengjiang Biota is the earliest Phanerozoic soft-bodied fossil assemblage offering the most complete snapshot of Earth's initial diversification, the Cambrian Explosion. Although palaeobiologic aspects of this biota are well understood, the precise sedimentary environment inhabited by this biota remains debated. Herein, we examine a non-weathered core from the Yu'anshan Formation including the interval preserving the Chengjiang Biota. Our data indicate that the succession was deposited as part of a delta influenced by storm floods (i.e., produced by upstream river floods resulting from ocean storms). Most Chengjiang animals lived in an oxygen and nutrient-rich delta front environment in which unstable salinity and high sedimentation rates were the main stressors. This unexpected finding allows for sophisticated ecological comparisons with other Burgess Shale-type deposits and emphasizes that the long-held view of Burgess Shale-type faunas as snapshots of stable distal shelf and slope communities needs to be revised based on recent sedimentologic advances.

Contrasting Early Ordovician assembly patterns highlight the complex initial stages of the Ordovician Radiation.

The Early Ordovician is a key interval for our understanding of the evolution of life on Earth as it lays at the transition between the Cambrian Explosion and the Ordovician Radiation and because the fossil record of the late Cambrian is scarce. In this study, assembly processes of Early Ordovician trilobite and echinoderm communities from the Central Anti-Atlas (Morocco), the Montagne Noire (France), and the Cordillera Oriental (Argentina) are explored. The results show that dispersal increased diachronically in trilobite communities during the Early Ordovician. Dispersal did not increase for echinoderms. Dispersal was most probably proximally triggered by the planktic revolution, the fall in seawater temperatures, changes in oceanic circulation, with an overall control by tectonic frameworks and phylogenetic constraints. The diachronous increase in dispersal within trilobite communities in the Early Ordovician highlights the complexity of ecosystem structuring during the early stages of the Ordovician Radiation. As Early Ordovician regional dispersal was followed by well-documented continental dispersal in the Middle/Late Ordovician, it is possible to consider that alongside a global increase in taxonomic richness, the Ordovician Radiation is also characterized by a gradual increase in dispersal.

Young coconut juice, a potential therapeutic agent that could significantly reduce some pathologies associated with Alzheimer's disease: novel findings.

Brains from ovariectomised (ovx) rats can display features similar to those observed in menopausal women with Alzheimer's disease (AD), and oestrogen seems to play a key role. Preliminary studies on young coconut juice (YCJ) have reported the presence of oestrogen-like components in it. The aim of the study was to investigate the effects of YCJ on the AD pathological changes in the brains of ovx rats. Rat groups included sham-operated, ovx, ovx+oestradiol benzoate (EB) and ovx+YCJ. Brain sections (4 µm) were taken and were immunostained with ß-amyloid (Aß) 1-42, glial fibrillary acidic protein (GFAP) (an intermediate neurofilament of astrocytes) and Tau-1 antibodies. Aß 1-42, GFAP and Tau-1 are considered as reliable biomarkers of amyloidosis, astrogliosis and tauopathy (neurofibrillary tangles), respectively, which in turn are characteristic features associated with AD. The serum oestradiol (E2) level was measured using a chemiluminescent immunoassay technique. YCJ restored the serum E2 to levels significantly (P < 0·001) higher than that of the ovx group, and even that of the sham group. Aß deposition was significantly (P < 0·0001) reduced in the cerebral cortex of the YCJ group, as compared with the ovx group and with the sham and ovx+EB groups (P < 0·01). A similar trend was observed in relation to GFAP expression in the cerebral cortex and to Tau-1 expression in the hippocampus. This is a novel study demonstrating that YCJ could have positive future implications in the prevention and treatment of AD in menopausal women.

Polydimethylsiloxane: An effective immune adjuvant and slow-release cytokine medium for local cancer treatment.

BACKGROUND AND AIM: Silicone oil or gel has well-defined chemotactic properties on monocytes and lymphocytes in vivo . It results in fibrotic reaction when spread into the human tissues either incidentally or purposely and can slowly release any physically-enclosed lyophilized compounds due to its viscosity. Our aim is to investigate whether polydimethylsiloxane could be considered as an effective medium in the local treatment of cancer. MATERIALS AND METHODS: Our study was conducted between January 2004 and December 2006 on 15 patients with various types of cancer. The criteria for selection included patients with locally-advanced tumor that was rapidly growing and life threatening and those who had poor quality of life and general wellbeing. The patients were already discharged from the cancer centre before joining the study, after they had already received their chemoradiation protocol. Once a week for one month, different areas of the tumor were injected with 0.25 ml of polydimethylsiloxane medical grade (viscosity: 350 centistokes at 30 degrees C), mixed with 300,000 units of lyophilized human IL-2. Tumor biopsies were taken before the study was started and one week after the last injection for the histopathological analysis of the percentage of severe inflammatory reaction using an image analysis system. CT scans of the tumor were taken before the injection cycle was started and one week after the last injection in order to determine the percentage change in the size of the tumor. The quality of life and general wellbeing of the patients was assessed at the beginning of the stud, and one week after the study was over by using the Karnofsky performance test. RESULTS: Our treatment was well tolerated by the patients. They had a significant improvement in their quality of life and general well being ( p = 0.0005). The prognosis of the patients before the beginning of the study ranged between 1 and 6 months, while their overall survival after treatment was between 2 and 12 months, with three patients still remaining alive. A significant decrease in the tumor size was observed at the end of the study in 12 patients ( p p 2 = 0.968; p CONCLUSION: Polydimethylsiloxane could be used as an effective cytokine medium in the local treatment of cancer. When injected inside the tumor, it is capable of creating and modulating an effective, slow and persistent antitumor immune response. Moreover, it is capable of improving the overall survival as well as the quality of life and general well being of the cancer patients.

The first pilot study on characteristics and practice patterns of Kuwaiti breast cancer patients.

Nongenetic breast cancer risk factors have never been evaluated in Kuwait. Accordingly, we aimed at examining these factors as well as the immune profile of the patients. Fifty stage I breast cancer patients and 50 age group-matched normal controls were assessed for the level of their peripheral blood lymphocyte subsets and for risk factors associated with their demographic and reproductive characteristics and with diet. The percentages of CD4+ T lymphocytes, CD4+:CD8+ ratio, and CD19+ B lymphocytes were significantly higher in the patients as compared to controls, while the percentages of CD8+ T lymphocytes and natural killer (CD56+) cells were significantly reduced. Risk factors associated with the disease included higher BMI, lack of regular exercise and physical activity in the past 5 years, early age at menarche, late age at first pregnancy, lack of previous information about breast cancer, hormonal therapy, and presence in Kuwait during the invasion/liberation. Other parameters included significantly more frequent consumption of carbohydrate, sweets, animal fat, and vegetable oil (margarine) and less frequent consumption of fresh vegetables and olive oil. This is the first study to highlight the environmental risk factors associated with breast cancer among the Kuwaiti women. We recommend introducing a nationwide campaign to further investigate these factors and to address them accordingly.

An innovative method to evaluate the suture compliance in sealing the surgical wound lips.

BACKGROUND AND AIM: The increasing number of surgical procedures performed with local anesthesia, followed by immediate patient discharge from the hospital, emphasizes the need for a tight waterproof suture that is capable of maintaining its tensile strength in the postoperative phase when the wound tumescence, edema due to the anesthetic drug, and surgical trauma disappear. Moreover, the issue of having an accurate surgical wound closure is very relevant in vivo in order to prevent hemorrhage and exogenous microbial infections. This study aimed at designing a new a lab technique that could be used for evaluating the best surgical material. Using such a technique, we compared the wound-lip-sealing properties of three commonly-used suture threads, namely polyurethane, polypropylene, and polyamide. MATERIALS AND METHODS: The mechanical properties of same-size suture threads made from polyurethane, polypropylene, and polyamide, were compared in order to define the one that possess the best elastic properties by being able to counteract the tension-relaxation process in the first 12 hours following surgery. The tension holding capacity of the suture materials was measured in both in vivo and in vitro experiments. The surface area of the scar associated with the three different suture threads was measured and compared, and the permeability of the three different suture threads was assessed at 0 minute, 2 minute, 4 minute, 6 minute, and 8 minute- interval. RESULTS: Results showed that polyurethane suture threads had significantly (P < 0.05) better tensile strength, elongation endurance before breakage, and better elasticity coefficient as compared to polypropylene and polyamide suture threads. Moreover, polyurethane suture threads were significantly (P < 0.05) more impermeable as compared to the other two suture thread types (polypropylene and polyamide). This impermeability was also associated with a tighter wound-lip-sealing ability, and with significantly (P < 0.05) less scar formation. CONCLUSION: Among the main concerns that surgeons, physicians, and patients often have is the development infection, oozing, and scar at the incision site following suturing. This always raises the question about which suture to use to avoid the above problems. This study provides evidence that the new technique developed in our lab could be used to compare the wound-lip sealing properties of different surgical suture threads. Using such a technique, the results show that polyurethane is significantly better than other commonly-used suture threads, like polypropylene and polyamide, in relation to wound sealing and scar formation.

Securebox: a multibiopsy sample container for specimen identification and transport.

OBJECTIVE: To describe an original multicompartment disposable container for tissue surgical specimens or serial biopsy samples (Securebox). STUDY DESIGN: The increasing number of pathology samples from a single patient required for an accurate diagnosis led us to design and manufacture a unique container with 4 boxes; in each box 1 or more biopsy samples can be lodged. A magnification lens on a convex segment of the plastic framework allows inspection of macroscopic details of the recovered specimens. We investigated 400 randomly selected cases (compared with 400 controls) who underwent multiple biopsies from January 2006 to January 2007 to evaluate compliance with the new procedure and detect errors resulting from missing some of the multiple specimens or to technical mistakes during the procedure or delivery that might have compromised the final diagnosis. RESULTS: Using our Securebox, the percentage of oatients whose diagnosis failed or could not be reached was O.5% compared to 4% with the traditional method (p = 0.0012). Moreover, the percentage of medical and nursing staff who were satisfied with the Securebox compared to the traditional methodwas 85% vs. 15%, respectively (p < 0.0001). The average number of days spent bto reach a proper diagnosis based on the usage of the Securebox was 3.38 +/- 1.16 SD compared to 6.76 +/- 0.52 SD with the traditional method (p < 0.0001). CONCLUSION: The compact Securebox makes it safer and easier to introduce the specimens and to ship them to the pathology laboratories, reducing the risk of error.

Pathobiological features of breast tumours in the State of Kuwait: a comprehensive analysis.

BACKGROUND: Breast cancer accounts for 30.3% of all cancer types in Kuwaiti women. Death occurs in approximately 43% of these patients. Our goal was to conduct a comprehensive analysis of the pathobiological characteristics of the tumours in an attempt to determine any particular trend that could be present. METHODS: One hundred and sixty-six cases were included in this study. All the pathology reports and paraffin blocks pertaining to these cases were collected. Four micrometer sections were taken from each block, and immunostaining against Her-2, ER, and PgR was performed. Both the proportion and intensity of immunostaining were scored according to the Allred's method, and typing of the tumour was done according the WHO criteria regarding tumour classification. Grading of invasive carcinomas was done according to the modified Bloom-Richardson-Elston's method, and tumour stage was determined according to the criteria set by the American Joint Committee on Cancer. RESULTS: The mean age of the patients below 55 years was 40, as compared to 68 for those above 55 (p < 0.0001). More than half of the cases were in the right breast, and were surgically treated by total mastectomy with axillary clearance. The majority of the tumours had irregular (stellate) margins, was invasive, and had a surrounding breast tissue of adenosis or fibrocystic type. Their mitotic index was 10-20 or >20 with a marked to moderate nuclear pleomorphism. They were mostly grade II or III, sized 2-5 or > 5 cm, had absent or scanty tumour lymphocytes, and were stage II or III. The in situ tumours were mainly ductal carcinoma (DCIS) of which comedo and cribriform were the major histological subtypes. The major histological subtypes of the invasive tumours were ductal-not otherwise specified, lobular, and tubular/cribriform. In this study, we also found a significant (p < 0.05) association between over expression of Her-2, lack of expression of ER and some of the characteristics mentioned above. CONCLUSION: Breast cancer in Kuwait seems to be more aggressive than what is currently seen in Europe, North America, Australia, and parts of Asia. Further investigations regarding the features observed in this study need to be performed.

Talin immunogold density increases in sciatic nerve of diabetic rats after nerve growth factor treatment.

BACKGROUND: Diabetic neuropathy is a debilitating disorder whose causation is poorly understood. Recent studies have shown significant reduction in the activity of nerve growth factor (NGF) and in the amount of talin cytoskeleton protein immunoreactivity in the perineurium in patients with diabetic neuropathy. OBJECTIVE: Since talin is involved in transmembrane connections between extracellular matrix and cytoskeleton, this study investigates the subcellular pattern of talin immunoreactivity and the effect of NGF treatment of diabetic rats on the distribution of talin in the sciatic nerve. MATERIALS AND METHODS: Post-embedding immunogold electron microscopy using monoclonal antibody against talin in combination with quantitative procedures was employed to localize talin-like immunoreactivity in the sciatic nerve of normal, diabetic and NGF treated diabetic rats. RESULTS: We found the highest densities of gold particles in the Schwann cells (139.6+/-5.6 particles/microm2) and in the fibroblasts (127.4+/-4.1 particles/microm2). A moderate amount of immunoreactivity was also present in the endothelial cells of vasa nervosa (32.3+/-9.1 particles/microm2). The myelinated and unmyelinated nerve fibers and the extracellular matrix profiles were not labeled (8.7+/-2.1 particles/microm2, 4.2+/-2.2 particles/microm2, 6.1+/-3.2 particles/microm2, 9.5+/-5.3 particles/microm2, respectively). The immunogold localization of talin in diabetic rats was significantly (p<0.001) reduced in Schwann cells (66.3+/-6.5 particles/microm2) and perineurial and epineurial fibroblasts (56.8+/-3.9 particles/microm2). Diabetic rats treated with NGF for 12 weeks showed significant (p<0.005) increase in talin-like immunogold density in Schwann cells and fibroblasts. Talin immunogold density in Schwann cells and fibroblasts increased approximately 68% and 58%, respectively, after NGF treatment. The endothelial cells of endoneurial and epineurial vessel walls showed no significant change in the talin-like immunogold particle density among control, diabetic and NGF treated diabetic animals. CONCLUSIONS: These results have shown that the administration of exogenous NGF may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy through maintaining the permeability of the barrier properties of the peripheral nerve.

Melanoma immunotherapy: past, present, and future.

The incidence of cancer and its related morbidity and mortality remain on the increase in both developing and developed countries. Cancer remains a huge burden on the health and social welfare sectors worldwide and its prevention and cure remain two golden goals that science strives to achieve. Among the treatment options for cancer that have emerged in the past 100 years, cancer vaccine immunotherapy seems to present a promising and relatively safer approach as compared to chemotherapy and radiotherapy. The identification of different tumour antigens in the last fifteen years using a variety of techniques, together with the molecular cloning of cytotoxic T lymphocytes (CTLs)- and tumour infiltrating lymphocytes (TILs)-defined tumour antigens allowed more refining of the cancer vaccines that are currently used in different clinical trials. In a proportion of treated patients, some of these vaccines have resulted in partial or complete tumour regression, while they have increased the disease-free survival rate in others. These outcomes are more evident now in patients suffering from melanoma. This review provides an update on melanoma vaccine immunotherapy. Different cancer antigens are reviewed with a detailed description of the melanoma antigens discovered so far. The review also summarises clinical trials and individual clinical cases in which some of the old and current methods to vaccinate against or treat melanoma were used. These include vaccines made of autologous or allogenic melanoma tumour cells, melanoma peptides, recombinant bacterial or viral vectors, or dendritic cells.