A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy

Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia‐inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors. © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Immunological appraisal of modified gluten to trim down celiac toxicity

The aim of the present research was to modify wheat gluten by binding methionine to gluten proteins to develop bread for celiac disease (CD) patients. The highest protein content, wet gluten content, dry gluten content and sodium dodecyl sulphate-sedimentation value were shown by the wheat variety AARI-11, therefore, it was selected for gluten modification. The bound methionine to gluten proteins was found increasing along the reaction time as the reaction proceeds and at a maximum near to 60 minutes and then it starts decreasing. The lowest immunoreactivity of the modified gluten was obtained near to 60 min of reaction at pH 10. The results for immunoglobulin A (IgA) index showed that the serum of each patient had positive IgA index to gliadins from unmodified gluten, but just sera of two patients had positive IgA index to gliadins from modified gluten and when these proteins were digested, the sera of no patient's serum had positive IgA reactivity. Among physical characteristics of breads 2 hours after baking, the specific volume of the modified gluten containing bread (4.13 ± 0.14 cm³/g) was lower than the control bread (4.59 ± 0.21 cm³/g). However, bread made with modified gluten had higher specific volumes than other gluten-free breads. Texture of the modified gluten was also affected by modification. Finally, the gluten content in the modified gluten bread was 79 ppm which is under the limits set by the Codex Alimentarius for food with reduced gluten content should have from 20 to 100 ppm. The study concludes that the incorporation of steric immensity into gluten proteins in order to shun immune recognition is the most promising approach to acquire wheat-based products that are tolerated by CD patients.     

Anatomical study of the communicating branches between the medial and lateral plantar nerves

The plantar areas of the foot have specific biomechanical characteristics and play a distinct role in balance and standing. For the forefoot surgeon, knowledge of the variations in the anatomy of communicating branches is important for plantar reconstruction, local injection therapy and an excision of interdigital neuroma. The anatomy of the communicating branches of the plantar nerves between the fourth and third common plantar digital nerves in the foot were studied in 50 adult men cadaveric feet. A communicating branch was present between the third and fourth intermetatarsal spaces nerves in all eight left feet and in six right feet (overall, 28%), and absent in 36 (72%). A communicating branch was found in 14 ft. Ten of the 14 communications were from the lateral to the medial plantar nerve. The length of the communicating branch ranged from 8 to 56 mm (average 16.4 mm) and its diameter was 0.2–0.6 times of the fourth common plantar digital nerve. The angle of the communicating branch with the common plantar digital nerve from which it originated was less than 30° in 11 ft, 30–59° in 27 ft, 60–80° in 8 ft, and more than 80° in 4 ft. Classification of the branch is based on the branching pattern of the communicating branch and explains variations in plantar sensory innervations. We think that the perpendicular coursing communicating branch is at higher risk to be severed during surgery.     

CT study on morphometry of frontal sinus

The aim of this study was to determine the prevalence and morphological characteristics of the frontal sinus in an adult population. This study was conducted retrospectively on paranasal CT scans in the axial and coronal planes of 300 cases (123 male and 177 female). The mean age was 40.74 +/- 13.34 (range 20-83). Measurements of the width, height and anteroposterior length for each sinus and total width were obtained from CT scans. Measurements were compared statistically with relation to side and sex. The cases were divided into subgroups according to age for each sex and each measurement parameter was also compared among the subgroups. All measurements tended to be larger on the left side and were significantly larger in males than females. There was a significant difference in the anteroposterior lengths of right and left sides in both males and females and height for males and width for females. In both sexes, the highest values of measurements were usually observed at the 31-40 age group and there was a tendency to decrease with aging. The larger diameters of the left frontal sinus imply that it may be more possibly violated during surgical interventions. Morphometric features differed significantly in the two sexes at different ages and comparison with previous studies presented great regional variability. The size of the frontal sinus was seen to be related to age and sex. The knowledge provided in the present study is useful for some surgical procedures and widens the anthropometric knowledge of humanity.     

In vitro sensitivity of Blastocystis hominis to garlic, ginger, white cumin, and black pepper used in diet

To determine the growth pattern and in vitro susceptibility of Blastocystis hominis to metronidazole (MTZ), garlic, ginger, white cumin, and black pepper. Stool specimens were collected from 16 irritable bowel syndrome (IBS) and 10 controls between July–November 2010. Stool microscopy and culture for B. hominis was performed. Drug susceptibility assays was done using 0.01 and 0.1 mg/ml of MTZ, garlic, ginger, white cumin, and black pepper. Effect was assessed on B. hominis culture after 48 h. Stool DNA was extracted using stool DNA extraction kit (Qiagen) and polymerase chain reaction (PCR) done using subtype-specific sequence-tagged-site primers. B. hominis genotype 3 and coinfection of 1 and 3 tended to grow well in culture compared to isolated type 1 infection. Exposed to MTZ at a concentration of 0.01 mg/ml, 38% (6/16) B. hominis from IBS did not grow in culture compared to 100% (10/10) of B. hominis from control (p = 0.001). When they were exposed to MTZ at 0.1 mg/ml, 56% (9/16) B. hominis from IBS did not grow in cultures compared to 100% (10/10) from control (p = 0.01). Forty-four percent (7/16) B. hominis from IBS did not grow in culture compared to 100% (10/10) B. hominis from control when exposed to garlic at a concentration of 0.01 mg/ml (p = 0.003) and following exposure to garlic at 0.1 mg/ml, 38% (6/16) B. hominis from IBS did not grow in cultures compared to 100% (10/10) from control (p = 0.001). B. hominis isolates from IBS had a cell count of 6,625 at a MTZ concentration of 0.01 mg/ml that reduced to 1,250 as MTZ concentration was increased to 0.1 mg/ml (p = 0.08). B. hominis from IBS with a mean cell count of 3 × 10⁵ at baseline decreased to 1 × 10⁴ when exposed to garlic at 0.01 mg/ml (p < 0.001) and to 1 × 10³ (p < 0.001) when garlic was 0.1 mg/ml. B. hominis from IBS cell count decreased to 1 × 10⁵ when exposed to white cumin at 0.01 mg/ml (p = 0.01) and to 1 × 10⁵ (p < 0.001) when white cumin was 0.1 mg/ml. Exposed to black pepper at 0.1 mg/ml, cell count of B. hominis from IBS decreased to 1 × 10⁵ (p = 0.01). B. hominis from IBS decreased to 1.3 × 10⁵ exposed to ginger at 0.01 mg/ml (p = 0.001). B. hominis isolates were mostly genotypes 3, type 1 and 3 coinfection, and non-typeable B. hominis isolates. B. hominis isolates from IBS mostly genotype 1 demonstrated an increased sensitivity to garlic at 0.01 mg/ml with a B. hominis cell count of 3,714 compared to 6,142 when exposed to 0.01 mg/ml of MTZ. However, this sensitivity did not increase as garlic concentration was increased to 0.1 mg/ml, for B. hominis cell count was 6,000 compared to 1,428 as MTZ was increased to 0.1 mg/ml.     

Neurobehavioral continuity from fetus to neonate

Neurobehavior represents development of the central nervous system (CNS). Fetuses and newborns exhibit a large number of endogenously generated motor patterns, among which general movements are often investigated pre- and post-natally. Spontaneous activity is probably a more sensitive indicator of brain dysfunction than reactivity to sensory stimuli while testing reflexes. Nutritional stress at critical times during fetal development can have persistent and potentially irreversible effects particularly on brain growth and function. Unfavorable intrauterine environment can affect adversely brain growth. All endogenously generated movement patterns from un-stimulated CNS might be observed as early as from the seven to eight weeks' gestation, with a rich repertoire of movements within the next two or three weeks, continuing for five to six months postnatally. It is still uncertain whether a new scoring system for prenatal neurological assessment will be adequate for the distinction between normal and abnormal fetuses in low-risk pregnancies. The continuity of behavioral patterns from prenatal to postnatal life might answer these intriguing questions.     

Navigational area of the cranio-orbital foramen and its significance in orbital surgery

The cranio-orbital foramen (COF) is located on the lateral wall of the orbit. It is a potential source of hemorrhage during deep lateral orbital dissection, since it functions as an anastomosis between the lacrimal artery and the middle meningeal artery. The aim of this study was to guide and facilitate the surgical procedures in the orbit, so as to determine a navigational area and the precise location of the COF and to standardize certain anatomical marks. The navigational area of the COF and topographical features were studied in 75 craniums with presented COF. 33 bilateral main COFs, 41 (18 on the right, 23 on the left) unilateral main COFs at the main cranium and 19 accessory COFs were studied for their navigational features on the orbit. The distances between the COF and the fronto-zygomatic suture, supraorbital notch, lateral angle of the superior orbital fissure (SOF) and Whitnall’s tubercle were measured. The mean distance of the COF from the fronto-zygomatic suture, supraorbital notch, lateral angle of the SOF and Whitnall’s tubercle was 26.3, 37.3, 92 and 27.1 mm, respectively. For the navigational area signs of the COF, areas of the orbit that form the transversal and vertical lines are generated on the reference points. Whilst the upper outer area of the orbit contains a potential bleeding risk, the bottom section of the outer column is identified as safe for the surgical operations of the lateral orbital wall. The fronto-zygomatic suture and Whitnall’s tubercle are recommended as the most reliable navigational landmarks for identifying the COF. Hence, the transversal and vertical orientation of the COF should be mastered by the surgeons reconstructing the anterior base of the skull and the orbit.