Basal cell adenoma-clinicopathological, immunohistochemical analysis and surgical considerations of a rare salivary gland tumor with review of literature.

INTRODUCTION: Basal cell adenoma (BCA) of the salivary glands is a rare benign salivary gland tumour. Differentiation of BCA from varied entities involving maxillofacial area is mandatory. AIM: To analyze the clinicopathological, histopathologic features, immunohistochemcal analysis and surgical considerations of this rare entity. MATERIALS AND METHODS: This study included 12 cases of BCA from archives of department reported over the period of 13 years. All the pertaining clinicopathologic features such as incidence, age, sex and site of lesions were assessed. Tissue sections were stained by using panel of immunohistochemical markers, i.e. Pan CK, CK 5/6 and S100, Calponin, p63, CD 117 and smooth muscle actin. RESULTS: BCA was observed in 26-52 years age group (mean age, 38.75 years) with female propensity of 7:5 male to female ratio. It is seen more commonly in parotid gland, followed by upper lip, buccal mucosa and palate. Solid type is the most common histopathologic type followed by tubular, membranous and trabecular. Only one case of membranous type of BCA showed recurrence. Pan CK, CK 5/6 showed strong immunoreactivity, calponin showed moderate staining, p63 and Ki-67 mild staining, whereas CD 117 and SMA showed negative immunostaining. CONCLUSION: Vigilant comprehensive analysis of all the pertaining clinicopathologic and histopathologic features and immunohistochemical analysis are required for differentiating from other lesions with basaloid differentiation having varying prognosis.

Antiulcer and gastric secretory activity of N-phthaloyl gamma-aminobutyric acid.

N-Phthaloyl gamma-aminobutyric acid, a new gamma-aminobutyric acid derivative synthesized in this laboratory, has been found to possess anticonvulsant, antinociceptive and antistress activities. Effects of this derivative on gastric lesions induced by aspirin and ethanol were studied in rats. N-Phthaloyl gamma-aminobutyric acid significantly inhibited both aspirin and alcohol ulceration. The ED50 in each case being 76.34 and 43.65 mg/kg i.p. respectively. The volume of gastric acid secretion was diminished but gastric mucus secretion was significantly enhanced. The antiulcer effect was blocked by bicuculline and 3-mercaptopropionic acid. We conclude that (a) N-phthaloyl gamma-aminobutyric acid possesses antiulcer activity (b) the new derivative is probably a non-specific gamma-aminobutyric acid receptor agonist (c) the observed activity may be due to a mucoprotective action.

Antiulcer and gastric secretory activity of N-octanoyl gamma-aminobutyric acid.

A new gamma-aminobutyric acid derivative synthesised in this laboratory, N-octanoyl gamma-aminobutyric acid was found to possess antinociceptive activity but no anticonvulsant activity. The effect of the compound on gastric lesions produced by aspirin, ethanol and stress in rats, was studied and the compound was found to possess effective antiulcer action. Even though, N-octanoyl gamma-aminobutyric acid did not produce a significant change in the volume of gastric acid secretion, however, it decreased the acidity and peptic activity and significantly enhanced the gastric mucus secretion.

Antinociceptive action of N-octanoyl GABA--a new GABA mimetic agent.

A new derivative of gamma-aminobutyric acid (GABA) was synthesized. The compound, N-octanoyl GABA (O-GABA), exhibited positive analgesic response in four different models in mice--tail immersion, hot plate, tail clip and acetic acid induced writhing. The antinociceptive activity was significantly blocked by picrotoxin but not by bicuculline or 3-mercaptopropionic acid. Naloxone failed to reverse the antinociceptive response of O-GABA but a synergistic action was observed with pethidine. Pretreatment with atropine significantly reduced the antinociceptive action of O-GABA. Biochemical tests revealed that O-GABA significantly increased brain GABA levels.

Anti-stress activity of N-phthaloyl gamma-aminobutyric acid in rats.

The effect of immobilization restraint stress (RS) on some biochemical and biophysical parameters in rats and their modulation by N-phthaloyl gamma-aminobutyric acid (P.GABA) was studied. RS did not affect the levels of serum Ca2+, inorganic phosphate, bilirubin, total protein, but caused insignificant increase of albumin level and significantly decreased the cholesterol level. This RS induced decrease of serum cholesterol level was reversed by prior treatment with P.GABA, while the albumin content showed a decrease. RS-induced a generalised increase in serum enzyme activity of lactate dehydrogenase (LDH), alkaline phsophatase (AIP), serum glutamate pyruvate transaminase (SGPT) and serum glutamate-oxaloacetate transaminase (SGOT). P.GABA normalised RS-induced increase of LDH and AlP activity, but it further enhanced SGOT and SGPT activities. In synaptosomal membranes, RS caused a decrease in clusterization and fluidity, but the thickness of the membrane increased as studied by fluorescence probes. Prior administration of P.GABA normalised the changes observed in the synaptic membrane.

Neuropharmacology of amide derivatives of P-GABA.

Three lipophilic amide derivatives of phthaloyl-GABA (P-GABA), namely gamma-phthalimido N-amyl butyramide (PGA), gamma-phthalimido-N-hexylbutyramide (PGH) and gamma-phthalimido N-phenylbutyramide (PGP), were synthesized and evaluated for their hypnotic and anticonvulsant activities in mice. Both PGA and PGH showed moderate hypnotic activity but PGP had no such action. Picrotoxin (0.08 mg/kg) a non-specific GABA antagonist completely abolished the hypnotic action of PGA in subconvulsive doses. Bicuculline (0.04 mg/kg) a GABAA antagonist, 3-mercaptopropionic acid (6 mg/kg) a GAD inhibitor at subconvulsive doses failed to neutralise the hypnotic action of PGA. On the other hand, PGA showed significant protection only against picrotoxin-induced convulsions, but was inactive against other convulsants tested. PGP which has no hypnotic activity, and has a mild anticonvulsant action in all the models except picrotoxin. A definite correlation was observed between the brain GABA and the hypnotic activity of PGA. However the present data indicate that the hypnotic and anticonvulsant activities are mediated probably through different brain GABA-ergic mechanisms.

Synthesis and anticonvulsant activity of N-phthaloyl GABA--a new GABA derivative.

A new gamma-aminobutyric acid derivative, N-phthaloyl GABA (P-GABA), was synthesised and its anticonvulsant activity was tested and compared with sodium valproate for efficacy against experimentally induced convulsions in mice. At a dose of 80 mg/kg, P-GABA rendered more protection than sodium valproate. ED50 of P-GABA and sodium valproate against bicuculline-induced convulsion was 96 and 301 mg/kg respectively in mice.

Effect of GABA analogues on various components of maximum electroshock-induced seizures in mice.

Out of fourteen compounds reported here only four [N-valproyl GABA (V.GABA), N-phthaloyl GABA (P.GABA), gamma-phthalimido N-amyl butyramide (PGA) and gamma-phthalimido N-phenyl butyramide (PGP)] gave significant protection to all the four components of maximal electroshock-induced seizures (MES) in mice. It appeared that substitution of either amino or carboxylic or both groups of gamma-aminobutyric acid (GABA) with bulkier groups like aliphatic or aromatic carbons usually produced effective anticonvulsant GABA derivatives. V.GABA and P.GABA were the most effective anticonvulsant GABA derivatives in protecting all the components of MES-induced seizures. They were 2.3 and 1.5 times potent than sodium valproate in molar ratio, but P.GABA has low therapeutic index when compared to V.GABA. The observed anticonvulsant activity may be due to enhanced GABA concentration in the CNS. Probably, the active compound (V.GABA) crossed the blood brain barrier and hydrolysed to GABA and valproic acid to bring about its anticonvulsant action.

Antinociceptive action of GABA-mimetic agent--N-phthaloyl GABA.

N-phthaloyl GABA (P-GABA), a nonselective GABA-ergic drug, showed positive analgesic response in four different models in mice, viz-tail immersion, tail clip, hot plate and writhing-induced by acetic acid. Antinociceptive ED50 (ip in mice) of P-GABA was lowest in tail immersion method (ED50 = 24.27, mg/kg). Though pethidine (10 mg/kg, ip) significantly potentiated the antinociceptive action of P-GABA (20 mg/kg, ip), pretreatment of naloxone (5 mg/kg, im) did not influence the same. Pretreatment with atropine (10 mg/kg, im), picrotoxin (0.08 mg/kg) and 3-mercaptopropionic acid (2 mg/kg) reduced the antinociceptive action of P-GABA significantly. But pretreatment with bicuculline (0.4 mg/kg), a specific GABA antagonist, did not reduce the antinociceptive action of P-GABA.

Antiulcer activity of N-phthaloyl GABA--a new GABA mimetic agent.

N-phthaloyl GABA (P. GABA) inhibited gastric ulceration induced by 3 hr restraint stress at 4 degrees C (CRS) in albino rats. Antiulcer activity of P. GABA was compared with sodium valproate and cimetidine. P. GABA, sodium valproate and cimetidine showed a dose dependent reduction of gastric ulceration. Pretreatment with GABA antagonists-bicuculline methiodide (0.5 mg/kg, im) or 3 mercaptopropionic acid (2 mg/kg, im) reversed the antiulcerogenic activity of both the drugs (P. GABA and sodium valproate). GABA antagonists as such did not induce gastric ulceration in normal rats.

Isolation and characterization of nonhistone proteins associated with DNase-II hypersensitive sites of Sarcoma-180 chromatin.

Limited digestion (2 min) of Sarcoma-180 nuclei by DNase-II released two nonhistone proteins from the hypersensitive sites of chromatin. The apparent molecular weights of these two proteins were 34 and 21 kDa. These proteins showed a moderate but specific inhibition in in vitro cell free transcription assay with native chromatin as template as opposed to no effect on native DNA transcription.

Inhibition of mast cell population by L-glutamine in aspirin-induced ulceration in rat stomach.

The effects of an amino acid L-glutamine on aspirin-induced gastric lesions as well as on the mast cell population were studied in rats. L-glutamine had a pronounced inhibitory effect on gastric lesions produced by oral aspirin administration. Aspirin-induced increase in the mast cell population of the stomach was also prevented. Parenteral administration of aspirain did not produce any significant damage to the gastric mucosa.

A comparative study on hypocholesterolaemic effect of allicin, whole germinated seeds of bengal gram and guggulipid of gum gugglu.

The daily use of allicin and whole germinated bengal gram seeds for 8 weeks led to a significant decrease in serum cholesterol levels in normal volunteers with no side effects. The standard reference, guggulipid therapy, significantly (p < 0.001) reduced the mean serum cholesterol level to 142.88 +/- 24.14 mg/100 mL from an initial status of 211.91 +/- 6.23 mg/100mL (32.36% +/- 12.48% fall). Allicin treatment significantly reduced the mean serum cholesterol level to 129.99 +/- 2.79 mg/100 mL from a pre-treatment value of 148.10 +/- 8. 81 mg/100mL, a fall of 13.36% +/- 4.64%. The serum cholesterol value was reduced to 135.62+/- 22.85 mg/100 mL from a pre-treatment value of 157.29 +/- 4.94 mg/100mL (17.15% +/- 9.94% fall) due to daily use of whole germinated bengal gram seeds. Hence the hypocholesterolaemic effects of allicin and whole germinated bengal gram seeds are comparable to the established standard reference, guggulipid. These two materials are herbal in origin and it is supposed to have a lesser risk-benefit ratio compared with other available synthetic drugs. The inclusion of these herbal products in the normal diet may be an alternative effective measure for hypercholesterolaemia.