Impact of Genetics on Neoadjuvant Therapy with Complete Pathological Response in Metastatic Colorectal Cancer: Case Report and Review of the Literature.

Treatment of colorectal metastatic cancer is still challenging, despite recent improvements in chemotherapy. A genetic cancer profile, such as the KRAS (Kirsten rat sarcoma) gene status, plays a key role in individualized tailored therapy. Molecular targeted therapy added to neo-adjuvant chemotherapy can achieve a better pathological response and prolong survival. Pathological complete response of colorectal cancer stage IV is rare. A 47-year-old female patient presented with rectal adenocarcinoma and three liver metastases (cT3d/4, N2, Ml). After seven cycles of Bevacizumab and CAPOX in neoadjuvant setting, we noted more than 70.0% regression of metastases and complete regression of the primary tumor. We performed low anterior resection of rectum and synchronous subsegmental resection of S3, because the other two lesions were not detectable. Pathology revealed complete response of the primary and also secondary tumors. After 8 months, diagnostic tests did not show any sign of recurrence and the remaining liver lesions disappeared. Colorectal cancer is a heterogeneous disease and it is necessary to identify patients who are at-risk of recurrence and suitable for neoadjuvant therapy. Genetic biomarkers play an important role in metastatic colorectal cancer treatment. Because of the mutated KRAS gene, Bevacizumab was added to cytotoxic therapy achieving a complete pathological response of primary tumor and metastasis. This case is unique because all reported cases with similar results, described staged surgery and one of reverse staged surgery, but with similar results. This neoadjuvant therapy has extraordinary results for colorectal cancer stage IV and can help disease-free and long-term survival.

Age-associated plasticity of α1-adrenoceptor-mediated tuning of T-cell development.

Alpha(1)-adrenoceptors (α(1)-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via α(1)-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as α(1)-AR expression, and 2) then the effects of 14-day-long treatment with the α(1)-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via α(1)-ARs due to increased NA availability and α(1)-AR thymocyte surface density in old rats. The second part of study supported this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCRαß(high) thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4+CD8- cells, including those showing a regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCRαß+cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161+TCRαß+cells. Thus, the study indirectly suggests an age-associated increase in the basal α(1)-AR-mediated inhibitory influence of NA on thymopoiesis.

Glucocorticoids, master modulators of the thymic catecholaminergic system?

There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight-1.day-1) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCRalphabetahigh thymocytes as revealed by two-way ANOVA; for CD4+CD8- F (1,20) = 10.92, P < 0.01; for CD4-CD8+ F (1,20) = 7.47, P < 0.05], a skewed thymocyte maturation towards the CD4-CD8+ phenotype, and consequently a diminished CD4+CD8-/CD4-CD8+ mature TCRalphabetahigh thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P < 0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis.

Expression of alpha1-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis.

The study was undertaken to explore: i) the presence of alpha(1)-adrenoceptors (AR) on thymic lymphoid and non-lymphoid cells and ii) their putative role in T-cell development. The expression of alpha(1)-AR on thymic cells was assessed using both immunohistochemistry and flow cytometric analyses, while their putative role in thymopoiesis was estimated by analyses of thymocyte proliferation and apoptosis, and major thymocyte subset distribution in adult rats subjected to 14-day-long treatment with the alpha(1)-AR blocker urapidil. The presence of alpha(1)-AR was demonstrated on both thymocytes (mainly less mature CD3(-) and CD3(low) cells) and thymic non-lymphoid cells (thymic epithelial cells and CD68-positive cells). Chronic treatment with urapidil increased the thymic weight and thymocyte number. The increase in thymocyte number might, at least partly, be related to an enhanced thymocyte proliferation. In addition, an altered thymocyte subset distribution was observed in these rats. The increase in the percentage of CD4+CD8+ double positive (DP) TCRalphabeta(-) thymocytes was accompanied by the reduction in that of CD4+CD8+ (DP) TCRalphabeta(low) cells, and divergent changes in the percentage of the most mature single positive (SP) TCRalphabeta(high) thymocytes. In urapidil-administered rats the percentage of CD4+CD8- SP TCRalphabeta(high) thymocytes was increased, while that of the CD4-CD8+ TCRalphabeta(high) was reduced, compared with controls. In addition, proportions of CD4+CD25+RT6.1- and CD161+TCRalphabeta+ regulatory cells were increased. Collectively, the results indicate that alpha(1)-AR are involved in complex network of neuro-thymic and intrathymic communications that provide fine tuning of both conventional effector and regulatory T-cell development.

Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

The role of gonadal hormones in induction and, particularly, maintenance/progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized (Cx) rats were greater than in age-matched control rats, sham Cx (Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate (the proportion of proliferating cells was 18.6 ± 0.7 percent in 2-month-old Cx (N = 5) vs 13.4 ± 0.3 percent (N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals (apoptotic thymocytes were 9.8 ± 0.9 percent in 2-month-old Cx (N = 5) vs 15.5 ± 0.3 percent (N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture (72.6 ± 1.2 percent in 10-month-old vs 9.8 ± 0.9 percent in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli (14.1 ± 0.2 percent in 10-month-old vs 18.6 ± 0.7 percent in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.

Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats.

The role of gonadal hormones in induction and, particularly, maintenance/progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized (Cx) rats were greater than in age-matched control rats, sham Cx (Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate (the proportion of proliferating cells was 18.6 +/- 0.7% in 2-month-old Cx (N = 5) vs 13.4 +/- 0.3% (N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals (apoptotic thymocytes were 9.8 +/- 0.9% in 2-month-old Cx (N = 5) vs 15.5 +/- 0.3% (N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture (72.6 +/- 1.2% in 10-month-old vs 9.8 +/- 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli (14.1 +/- 0.2% in 10-month-old vs 18.6 +/- 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.

Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats.

Age-related increase in the density of thymic noradrenergic fibres and noradrenaline (NA) concentration is proposed to be associated with thymic involution and altered thymopoiesis. To test this hypothesis thymocyte differentiation/maturation and thymic structure were studied in 18-month-old male Wistar rats subjected to 14-day-long propranolol (P) blockade of beta-adrenoceptors (beta-ARs). The treatment primarily resulted in changes in the T-cell receptor (TCR)-dependent stages of thymopoiesis, which led to an increase in both the relative and absolute numbers of the most mature single positive (SP) CD4(+)CD8(-) (including cells with the CD4(+)CD25(+) regulatory phenotype) and CD4(-)CD8(+) TCRalphabeta(high) thymocytes. Accordingly, in the thymi of these rats an increase in both numerical density and absolute number of medullary thymocytes encompassing mainly the most mature SP cells was found. These findings, together with an increase in the thymocyte surface expression of the regulatory molecule Thy-1 (CD90) (implicated in negative regulation of TCRalphabeta-dependent thymocyte selection thresholds) in the same rats, may suggest increased positive/reduced negative thymocyte selection. Collectively, the results indicate that a decline in thymic efficiency in generating both conventional and regulatory T cells, and consequently in immune function, in aged rats may be, at least partly, attenuated by long-term blockade of beta-ARs with P.

Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level.

To test putative interdependence in the ontogenesis of the hypothalamic-pituitary-gonadal and thymic-lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4(-)CD8(-)TCRalphabeta(-) triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCRalphabeta(-), TCRalphabeta(low) and TCRalphabeta(high)) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCRalphabeta(low) developmental stage accompanied by an increased positive/ reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCRalphabeta(high) thymocyte subsets were reduced, while their numbers were increased (CD4(+)CD8(-)) or unaltered (CD4(-)CD8(+)), coupled with results demonstrating an increased level of CD4(-)CD8(+) cells without changes in that of CD4(+)8(-) cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCRalphabeta(high) thymocytes towards CD4(-)8(+) TCRalphabeta(high) cells followed by increased emigration of the mature cells and (ii) decelerated differentiation and maturation towards CD4(+)8(-)TCRalphabeta(high) cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4(+)CD25(+)Foxp3(+) regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.

Morphometrical characteristics of age-associated changes in the thymus of old male Wistar rats.

In order to provide a morphometrical description of the changes in the aged rat thymus and to relate them to apoptotic and proliferative activity of thymocytes, the thymuses from 3- and 18-month-old male Wistar rats and the percentages of bromodeoxyuridine-incorporating and apoptotic cells in cultures of thymocytes were assessed by stereological analysis and flow cytometry, respectively. In old rats the volume of lymphoepithelial thymic tissue is markedly reduced, reflecting a sharp decrease in the total number of thymocytes. A reduction in the proliferative capacity of thymocytes and increase in their susceptibility to apoptosis are, most likely, primarily responsible for a 7-fold reduction in thymic cellularity in old animals. Furthermore, only the volume of cortical compartment was affected by aging, while that of medulla, despite of reduced cellularity, was not significantly altered. The loss of functional tissue in aged thymus is compensated by a substantial increase in the volume of inter-lobular connective and adipose tissue, so the thymic weight remained unaltered in old rats. These results suggest that thymus of aged Wistar rats exhibits morphological characteristics similar to those found in aged human thymus and thus may serve as an animal model for further investigations of thymus-related changes in immunological aging.

Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis.

Adult male Wistar rats were subjected to propranolol (P, 0.40 mg/100 g/day) or saline (S) administration (controls) over 14 days. The expression of major differentiation molecules on thymocytes and Thy-1 (CD90) molecules, which are shown to adjust thymocyte sensitivity to TCRalphabeta signaling, was studied. In addition, the sensitivity of thymocytes to induction of apoptosis and concanavalin A (Con A) signaling was estimated. The thymocytes from P-treated (PT) rats exhibited an increased sensitivity to induction of apoptosis, as well as to Con A stimulation. Furthermore, P treatment produced changes in the distribution of thymocyte subsets suggesting that more cells passed positive selection and further differentiated into mature CD4+ or CD8+ single positive (SP) TCRalphabeta(high) cells. These changes may, at least partly, be related to the markedly increased density of Thy-1 surface expression on TCRalphabeta(low) thymocytes from these rats. The increased frequency of cells expressing the CD4+25+ phenotype, which has been shown to be characteristic for regulatory cells in the thymus, may also indicate alterations in thymocyte selection following P treatment. Inasmuch as positive and negative selections play an important role in continuously reshaping the T-cell repertoire and maintaining tolerance, the hereby presented study suggests that pharmacological manipulations with beta-AR signaling, or chemically evoked alterations in catecholamine release, may interfere with the regulation of thymocyte selection, and consequently with the immune response.

Effects of extremely low-frequency magnetic field in the brain of rats.

An extremely low-frequency magnetic field (50 Hz, 0.5 mT) was used to investigate its possible effect on the brain of adult male Wistar rats following a 7-day exposure. The control rats were sham-exposed. Superoxide dismutase activities and production of superoxide radicals, lipid peroxidation, and nitric oxide were examined in the frontal cortex, striatum, basal forebrain, hippocampus, brainstem, and cerebellum. Significantly increased superoxide radical contents were registered in all the structures examined. Production of nitric oxide, which can oppose superoxide radical activities, was significantly increased in some structures: the frontal cortex, basal forebrain, hippocampus, and brainstem. Augmentation of lipid peroxydation was also observed, with significance only in the basal forebrain and frontal cortex, in spite of the significantly increased superoxide dismutase activities and nitric oxide production in the basal forebrain, and increased production of nitric oxide in the frontal cortex. The results obtained indicate that a 7-day exposure to extremely low-frequency magnetic field can be harmful to the brain, especially to the basal forebrain and frontal cortex due to development of lipid peroxidation. Also, high production of superoxide anion in all regions may compromise nitric oxide signaling processes, due to nitric oxide consumption in the reaction with the superoxide radical.

Repeated exposure to low-level extremely low frequency-modulated microwaves affects baseline and scopolamine-modified electroencephalograms in freely moving rats.

PURPOSE: To compare in the electroencephalogram of rats the effects of scopolamine (an acetylcholine receptor antagonist) alone and after repeated exposure to low-level microwaves modulated at extremely low frequency. MATERIALS AND METHODS: Averaged frequency spectra (0.5-30 Hz) of the electroencephalogram were studied in freely moving rats with carbon electrodes implanted into the somatosensory cortex. The rats were repeatedly (3 days, 30 min day(-1)) exposed to low-intensity (approximately = 0.3 mW cm(-2)) microwaves (915 MHz, 20-ms pulse duration), amplitude modulated (square-wave) at extremely low frequency (4 Hz). RESULTS: The exposure to extremely low frequency microwaves alone significantly enhanced the fast electroencephalographic rhythms (18-30 Hz). This effect was observed neither in subsequent sham-exposure experiment nor in radiation-naïve animals. In the microwave-exposed rats, scopolamine (0.1 mg kg(-1), subcutaneously) did not cause a slowing in the electroencephalogram that was shown in non-exposed rats. A similarity between the scopolamine-induced electroencephalogram effect in the microwave-exposed rats and that of physostigmine (enhancing the acetylcholine level in the brain) in radiation-naïve animals was noted. This paradoxical phenomenon stimulates new experimentation for understanding its mechanism(s). CONCLUSIONS: The data obtained provide additional evidence that repeated low-level exposure to extremely low frequency microwaves can modify an activity of cholinergic system in the brain.

Opposite effects of dexamethasone and ACTH on the adrenal cortex response to ethane dimethanesulphonate (EDS).

Recently we have reported that ethane dimethane-sulphonate (EDS), the Leydig cell cytotoxin, caused marked atrophy of the adrenal cortex of adult male rats. The aim of this work was to examine whether a 9-day treatment with dexamethasone (0.25 mg/kg/d) or ACTH (40 IU/kg/d), which started 4 days prior to administration of a single dose of EDS (75 mg/kg), influenced the response of the inner adrenocortical zones to the toxin. On day 15 after administration of EDS, adrenal weight was significantly decreased in saline treated rats, but glandular and serum corticosterone levels were not altered. In dexamethasone-suppressed rats, the effect of EDS was augmented; an additional decrease in adrenal weight was accompanied by reduced adrenal and serum corticosterone levels. In ACTH-treated animals EDS was ineffective. These results demonstrate that the deleterious effects of EDS on rat adrenal cortex can be prevented by ACTH and potentiated by dexamethasone.

beta-Adrenergic receptor manipulation and acid phosphatase and zinc levels in the ventral prostate of the adult rat.

The influence of 15-day treatments with the beta-adrenergic receptor agonist isoproterenol (120 micrograms/kg/d) or the antagonist propranolol (1.00 mg/kg/d) on acid phosphatase and zinc levels in the ventral prostate was examined in intact rats, rats simultaneously injected with dexamethasone (0.25 mg/kg/d) and animals chemically castrated with a single dose of ethane dimethanesulphonate (75 mg/kg). Isoproterenol-treatment significantly increased acid phosphatase concentration in the ventral prostate of intact rats, whereas propranolol prevented a glandular zinc loss induced by dexamethasone administration. These results demonstrate that the levels of both biochemical parameters in the prostate can be altered by beta-adrenergic receptor manipulation. The responsiveness of the two secretory processes is different and depends on the functional status of the ventral prostate.

[Ultrasonically-guided percutaneous needle biopsy in the diagnosis of malignant abdominal diseases]. / Perkutana iglena biopsija vodjena ultrazvukom u dijagnostici malignih oboljenja u abdomenu.

In 3-year period 340 percutaneous ultrasonographically guided needle biopsies of abdominal organs and tissues were performed in suspected neoprocesses. Positive cytologic results were obtained in 77.6% and histological in 74.8% of patients. These results were obtained thanks to good choice of a bioptic needle and the technique of performing percutaneous needle biopsy under ultrasonographic control and sometimes in combination with radioscopy, too. Experience of both a biopsy performer and a cytologist or histologist with this kind of material is of great importance. Thanks to early histologic diagnosis, made in this way, percutaneous biopsy is classified as a high sensitive method and as such it forces on to be one of the first methods in algorithm of diagnostic procedures. Even the aim of this paper is to point out not only the authors ultrasonographic experience but also reliability, simplicity and safety of percutaneous guided needle biopsies, what excludes the necessity for more difficult and more expensive diagnostic procedures significantly reducing the examination.

[Correlation of cytologic and pathohistologic findings in ultrasonically-guided thin-needle biopsy of abdominal and retroperitoneal organs]. / Korelacija citoloskih i patohistoloskih nalaza biopsija tankom iglom abdominalnih i retroperitonealnih organa pod kontrolom ultrazvuka.

The ultrasonically guided fine needle biopsy is cheap, very sensitive and specific method for the diagnosis of nonpalpable deep-seated lesions. During 1992 in the institute of Radiology of Military Medical Academy in Belgrade 87 biopsies of abdominal and 81 biopsies of retroperitoneal organs were performed for the cytological and histopathologic analysis. Deficient material was obtained in 15.4% of the cases. A good correlation between cytologic and histopathologic findings was observed, with diagnostic concordance in 90.8%. In 9 cases with falsely positive cytological diagnosis at the first examination, the diagnosis of malignancy was later confirmed by other diagnosis procedures. Diagnostic difficulties and the significance of adequate biopsy were particularly stressed.

[Percutaneous needle biopsy of the distal part of the choledochal duct]. / Perkutana iglena biopsija distalnog dela duktusa holedokusa.

The indication for the biopsy was the finding of stenosis of uncertain etiology even after the endoscopy and the attempt of endoscopic or brush biopsy. The experiences with needle biopsy in 6 patients were presented in the study. The biopsy was done with the needles with diameter less than 1 mm (Chiba needle 0.6-0.95 mm), Otto-cut 0.8 mm and Vacu-cut 0.8 mm. Percutaneous cholangiography that was firstly performed, showed the site of stenosis of common bile duct distal part and simultaneously the other structures of interest for biopsy performance. The needle was guided under radioscopic control in one attempt. In that way, the precise diagnosis of pathologic process, which induced the obstruction in the early disease stage was made in all six patients. On the basis of cited results, the percutaneous needle biopsy was found to be efficient and safe method to reveal the type of lesion in this region, if necessary conditions existed. Percutaneous needle biopsy is a very valuable method, less invasive and less expensive compared to the surgical biopsies and other methods. It demonstrated reliable results in our conditions.

[Pharmacotherapy childhood asthma]. / Farmakoterapija decje astme.

The drugs which are used today in medical treatment of asthma can be divided into two groups. The first group contains corticosteroides, as antiinflammatory agents. The second group contains bronchodilatators, usually used as symptomatic medicaments, and the third group are asthma--profilactics. The mechanism of activity, doses for children and unwanted effects are briefly presented for eah of these three groups. The principles of the International consensus about medical treatment of childhood asthma are presented in the second part of this paper.

HPLC determination of sodium cromoglycate in pharmaceutical dosage forms.

A reversed-phase high-performance liquid chromatography (HPLC) method is described for the determination of sodium chromoglycate (SCG) in bulk drug and pharmaceutical dosage forms (capsules, solutions, gels). Aliquots were chromatographed on C18 columns using methanol: phosphate buffer (50:50 v/v) at pH 2.3 as the mobile phase. Detection was performed at 326 nm with a linear range of 0.05-0.5 microgram/ml (r = 0.9999). Recovery values ranged from 99.21 to 106.31% (N = 9). The proposed method is rapid and simple, free from interference by excipient and degradation products, and can be recommended for routine control analysis of sodium chromoglycate commercial products and magistral formulations.

Morphometric analysis of mandibular canal: clinical aspects.

Results of morphometric analysis of the mandibular canal (MC), carried out on 105 conserved mandibles, 70 being dentate and 35 edentate, was performed. The analysis was carried out on consecutive sections, at mutual intervals of 0.5 cm. In the mandibular ramus sections were carried out obliquely, approximately in the frontal plane, and horizontally, from mandibular foramen to the lowest region of the vertical part of the MC (all together two sections). In the mandibular corpus, consecutive transversal sections were carried out between existing teeth, or at mutual intervals of 0.5 cm in edentate regions. The obtained results pointed out the very close relationship between the MC and lingual cortical plate of the mandibular ramus. In its horizontal part, the average diameter of the MC was 2.6 mm. It was situated more lingually in the molar region; towards the front, it approached the vestibular cortical plate, being closest to it in the region of the second premolar. Similar relationships of the MC and both cortical plates existed in edentate jaws. Relationships of the MC and tooth root apices varied; however, the MC was closest to the apices of the third molar. Mesially from the mental foramen, a clearly defined incisive canal was present in 92% of the dentale mandibles, but only in 31% of the edentate ones. The nearest to the incisive canal was the apex of the first premolar. The authors point out the importance of presented results in everyday practice, especially in oral and maxillofacial surgery.(ABSTRACT TRUNCATED AT 250 WORDS)