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The adenine nucleotide translocation in mitochondria has previously been established as an exchange between exogenous and endogenous adenine nucleotides across the inner membrane. The specificity and the control of the exchange are examined with the following major results: The adenine nucleotide translocation is relatively specific for exogenous ADP and ATP, AMP being nearly inactive. Among other nucleotides tested, only dADP and dATP exchange with a noticeable activity. In the controlled state ADP exchanges 2–4 times faster than ATP. If simultaneously added, ADP and ATP compete for the exchange, with ADP being about tenfold more active than ATP. The specificity of the exit of adenine nucleotides in the exchange is similar to the specificity of the entrance with the difference that ADP and ATP are released with equal activity in proportion to their intramitochondrial content. AMP is released only after a slow conversion to ADP. Therefore the short time exchange is limited by the endogenous content of ADP plus ATP. The exchange is influenced by the metabolic state of the mitochondria. The ATP exchange is more variable than the ADP exchange. Two effects are elucidated: (a) the influence of the metabolic state on the relative content of AMP which inhibits both the ADP and ATP exchange (b) the coupling of the energy transfer system which inhibits only the ATP exchange. An example for case (a) is the inhibition of the ADP and ATP exchange by arsenate and an example for case (b) is the strong increase of the ATP exchange on uncoupling. The following effects are relevant to the mechanism of the control of the exchange by ATP. The stimulation of the ATP exchange by uncoupler has the same concentration dependence as the uncoupling of oxidative phosphorylation (Km [CCP] = 0.08 μM, where CCP = carbonyl‐cyanide‐phenylhydrazone). Oligomycin does not abolish the uncoupler effect on the ATP exchange. “Endogenous uncoupling” on aging of mitochondria also stimulates the ATP exchange. Valinomycin plus K+ only slightly stimulate the ATP exchange. Anaerobiosis stimulates the ATP exchange to a smaller extent than uncoupling.In competition with ADP the effects of energy transfer on ATP exchange are more strongly revealed. On uncoupling the more than tenfold preference for ADP is fully abolished. It is concluded that basically the exchange for ADP and ATP has equal specificity in forward and reverse reaction. In the controlled state a superimposed force makes the specificity asymmetric and inhibits the entrance of ATP. This control of the ATP exchange is concluded to be based on the anionic character of the adenine nucleotides. Thus the ATP4‐ex–ADP3‐in exchange is inhibited unless the charge difference is compensated for by an uncoupler stimulated H+ movement across the membrane. Furthermore an electric potential gradient appears to be effective in the controlled state which is abolished on uncoupling.

The adenine nucleotide translocation in mitochondria has previously been established as an exchange between exogenous and endogenous adenine nucleotides across the inner membrane. The specificity and the control of the exchange are examined with the following major results: The adenine nucleotide translocation is relatively specific for exogenous ADP and ATP, AMP being nearly inactive. Among other nucleotides tested, only dADP and dATP exchange with a noticeable activity. In the controlled state ADP exchanges 2–4 times faster than ATP. If simultaneously added, ADP and ATP compete for the exchange, with ADP being about tenfold more active than ATP. The specificity of the exit of adenine nucleotides in the exchange is similar to the specificity of the entrance with the difference that ADP and ATP are released with equal activity in proportion to their intramitochondrial content. AMP is released only after a slow conversion to ADP. Therefore the short time exchange is limited by the endogenous content of ADP plus ATP. The exchange is influenced by the metabolic state of the mitochondria. The ATP exchange is more variable than the ADP exchange. Two effects are elucidated: (a) the influence of the metabolic state on the relative content of AMP which inhibits both the ADP and ATP exchange (b) the coupling of the energy transfer system which inhibits only the ATP exchange. An example for case (a) is the inhibition of the ADP and ATP exchange by arsenate and an example for case (b) is the strong increase of the ATP exchange on uncoupling. The following effects are relevant to the mechanism of the control of the exchange by ATP. The stimulation of the ATP exchange by uncoupler has the same concentration dependence as the uncoupling of oxidative phosphorylation (Km [CCP] = 0.08 μM, where CCP = carbonyl‐cyanide‐phenylhydrazone). Oligomycin does not abolish the uncoupler effect on the ATP exchange. “Endogenous uncoupling” on aging of mitochondria also stimulates the ATP exchange. Valinomycin plus K+ only slightly stimulate the ATP exchange. Anaerobiosis stimulates the ATP exchange to a smaller extent than uncoupling.In competition with ADP the effects of energy transfer on ATP exchange are more strongly revealed. On uncoupling the more than tenfold preference for ADP is fully abolished. It is concluded that basically the exchange for ADP and ATP has equal specificity in forward and reverse reaction. In the controlled state a superimposed force makes the specificity asymmetric and inhibits the entrance of ATP. This control of the ATP exchange is concluded to be based on the anionic character of the adenine nucleotides. Thus the ATP4‐ex–ADP3‐in exchange is inhibited unless the charge difference is compensated for by an uncoupler stimulated H+ movement across the membrane. Furthermore an electric potential gradient appears to be effective in the controlled state which is abolished on uncoupling.

1. The gastroprotective activity of two azomethine prodrugs of (R)-alpha-methylhistamine was examined in lesions induced by absolute ethanol (1 ml/rat intragastrically for 1 h). 2. Pretreatment with (R)-alpha-methylhistamine as well as with the prodrugs (30 and 100 mg/kg intragastrically [IG]) significantly reduced macroscopically visible lesions caused by ethanol, with protection being almost complete at 100 mg/kg. 3. Histologically, in rats pretreated with the three compounds at a dose of 100 mg/kg, the evidence of damage was rare, with the appearance of gastric mucosa being similar in the different groups. 4. Present results are suggestive of a local component in the protective activity of (R)-alpha-methylhistamine.

1. The gastroprotective activity of two azomethine prodrugs of (R)-alpha-methylhistamine was examined in lesions induced by absolute ethanol (1 ml/rat intragastrically for 1 h). 2. Pretreatment with (R)-alpha-methylhistamine as well as with the prodrugs (30 and 100 mg/kg intragastrically [IG]) significantly reduced macroscopically visible lesions caused by ethanol, with protection being almost complete at 100 mg/kg. 3. Histologically, in rats pretreated with the three compounds at a dose of 100 mg/kg, the evidence of damage was rare, with the appearance of gastric mucosa being similar in the different groups. 4. Present results are suggestive of a local component in the protective activity of (R)-alpha-methylhistamine.

Abstract An orange and an apple juice each containing 250–385 ppm tin were under suspicion of having caused an outbreak of food poisoning in Kuwait in 1967 but did not cause any toxic signs when fed to pigeons, cats and dogs. One cat out of 11 vomited when fed an orange juice containing 540 ppm tin derived from the container, and with juices containing 1370 ppm tin, 20–30% of the cats vomited but none of the dogs was affected. Fruit juices containing 2000 ppm tin caused vomiting in up to 40% of the cats. Modification of orange juices with a high tin content by addition of nitrate or ethanol or by adjustment of the pH from 3 to 6 did not affect the incidence of vomiting. No toxic signs were produced in rats given fruit juices containing added tin salts up to a level of 995 ppm or in rats and cats given aqueous solutions of tin salts (up to 1200 ppm tin) in citric acid. Solid foods containing tin derived from the containers up to the highest level obtainable (470 ppm) had no toxic effect when fed to dogs and cats. Five human volunteers showed no toxic signs after drinking fruit juices containing 498, 540 or 730 ppm tin derived from the containers, but all five had some gastro-intestinal disturbance after drinking a fruit juice containing 1370 ppm tin. A repeat experiment with the latter juice had no effect in four of the volunteers and only mild symptoms in the fifth. In rats and cats, there was no evidence of tin absorption 24 hr after ingestion of fruit juices containing high levels of tin. No tin was recovered from the urine and in the rats 99% was recovered from the faeces. Only minute amounts of tin could be found in the body, apart from the alimentary tract, of a rat that had been given orange juice with a high tin content ad lib. instead of drinking water for 7 days. It is concluded that toxic signs follow the drinking of tin-containing fruit juices by man and cats only with tin levels of approximately 1400 ppm and above, that there is no evidence from these experiments that toxicity is due to the absorption of tin and that the most likely cause is local irritation of the mucous membrane of the alimentary tract.

Abstract An orange and an apple juice each containing 250–385 ppm tin were under suspicion of having caused an outbreak of food poisoning in Kuwait in 1967 but did not cause any toxic signs when fed to pigeons, cats and dogs. One cat out of 11 vomited when fed an orange juice containing 540 ppm tin derived from the container, and with juices containing 1370 ppm tin, 20–30% of the cats vomited but none of the dogs was affected. Fruit juices containing 2000 ppm tin caused vomiting in up to 40% of the cats. Modification of orange juices with a high tin content by addition of nitrate or ethanol or by adjustment of the pH from 3 to 6 did not affect the incidence of vomiting. No toxic signs were produced in rats given fruit juices containing added tin salts up to a level of 995 ppm or in rats and cats given aqueous solutions of tin salts (up to 1200 ppm tin) in citric acid. Solid foods containing tin derived from the containers up to the highest level obtainable (470 ppm) had no toxic effect when fed to dogs and cats. Five human volunteers showed no toxic signs after drinking fruit juices containing 498, 540 or 730 ppm tin derived from the containers, but all five had some gastro-intestinal disturbance after drinking a fruit juice containing 1370 ppm tin. A repeat experiment with the latter juice had no effect in four of the volunteers and only mild symptoms in the fifth. In rats and cats, there was no evidence of tin absorption 24 hr after ingestion of fruit juices containing high levels of tin. No tin was recovered from the urine and in the rats 99% was recovered from the faeces. Only minute amounts of tin could be found in the body, apart from the alimentary tract, of a rat that had been given orange juice with a high tin content ad lib. instead of drinking water for 7 days. It is concluded that toxic signs follow the drinking of tin-containing fruit juices by man and cats only with tin levels of approximately 1400 ppm and above, that there is no evidence from these experiments that toxicity is due to the absorption of tin and that the most likely cause is local irritation of the mucous membrane of the alimentary tract.

AbstractThe efficacy of thyroid (FNAB) processed by liquid‐based cytology (LBC) in Hashimoto's Thyroiditis (HT) in two reference periods, is evaluated. The morphologic features of 820 cases with both methods and the cyto‐histological comparison are analyzed. The diagnosis of hyperplastic nodules (HN) in HT, its mimickers especially in presence of oxyphilic cells and the role of immunocytochemistry (IHC) are studied.150 cases of HT processed by conventional smear (CS) in 1996–98 and 670 with LBC in 2005–2007,were included. The majority of FNAB were carried out under USguidance and fixed with ethyl alcohol for the CS. LBC material was rinsed in the Cytolit solution, processed according to the manufacturer's recommendations. Among the 150 CS, 83 were HT while 67 were HN in HT; in the second triennium 245 LBC were HT and 425 were HN in HT. In the first period a follow‐up (including a second FNA or surgery) was done in 92 cases, in the second period in 116.In the surgical group 97.1% in the first period were benign (all HT and 34/36 HN) and 2.8% malignant(all HN). In 2005–2007, 94% were benign (15 HT and 45/49 HN) and 6%malignant. Thirty HN from the second triennium had ICC for HBME‐1 and Galectin‐3 resulting negative in 93.5%. Among these cases, 10 had a benign histology and a concordant negative ICC.LBC can be used as a valid method for HT, especially for the possible application of ICC to HN, and it allows a correct preoperative selection of lesions Diagn. Cytopathol. 2011; © 2011 Wiley‐Liss, Inc.

AbstractThe efficacy of thyroid (FNAB) processed by liquid‐based cytology (LBC) in Hashimoto's Thyroiditis (HT) in two reference periods, is evaluated. The morphologic features of 820 cases with both methods and the cyto‐histological comparison are analyzed. The diagnosis of hyperplastic nodules (HN) in HT, its mimickers especially in presence of oxyphilic cells and the role of immunocytochemistry (IHC) are studied.150 cases of HT processed by conventional smear (CS) in 1996–98 and 670 with LBC in 2005–2007,were included. The majority of FNAB were carried out under USguidance and fixed with ethyl alcohol for the CS. LBC material was rinsed in the Cytolit solution, processed according to the manufacturer's recommendations. Among the 150 CS, 83 were HT while 67 were HN in HT; in the second triennium 245 LBC were HT and 425 were HN in HT. In the first period a follow‐up (including a second FNA or surgery) was done in 92 cases, in the second period in 116.In the surgical group 97.1% in the first period were benign (all HT and 34/36 HN) and 2.8% malignant(all HN). In 2005–2007, 94% were benign (15 HT and 45/49 HN) and 6%malignant. Thirty HN from the second triennium had ICC for HBME‐1 and Galectin‐3 resulting negative in 93.5%. Among these cases, 10 had a benign histology and a concordant negative ICC.LBC can be used as a valid method for HT, especially for the possible application of ICC to HN, and it allows a correct preoperative selection of lesions Diagn. Cytopathol. 2011; © 2011 Wiley‐Liss, Inc.