Recent studies showed that mesenchymal stem cells derived from adipose tissue can promote tumour ... more Recent studies showed that mesenchymal stem cells derived from adipose tissue can promote tumour progression, raising some concerns regarding their use in regenerative medicine. In this context, we co-cultured either SAOS2 osteosarcoma or MCF7 breast cancer cells with human adipose stem cells (hASCs), in order to evaluate potential effects of cancer cells on hASCs differentiation, in vitro and in vivo. In this study we observed that both SAOS2 and MCF7 cell lines induced an increase in hASCs proliferation, compared to hASCs alone, but, surprisingly, neither changes in the expression of CD90, CD29, CD324 and vimentin, nor variations in the Twist and Slug mRNAs were detectable. Noteworthy, SAOS2 and MCF7 cells induced in hASCs an upregulation of CD34 expression and stemness genes, including OCT3/4, Nanog, Sox2 and leptin, and a decrease in angiogenic factors, including CD31, PDGFα, PDGFRα, PDGFRβ and VEGF. SMAD and pSMAD2/3 increased only in hASCs alone. After 21 days of co-culture, hASCs differentiated both in adipocytes and endothelial cells. Moreover, co-injection of MCF7 cells with hASCs led to the formation of a highly vascularized tumour. Taken together our findings suggest that mesenchymal stem cells, under tumour cell induction, do not differentiate in vitro or facilitate the angiogenesis of the tumour in vivo, thus opening interesting new scenarios in the relationship between cancer and stem cells. These findings may also lead to greater caution, when managing autologous fat grafts in cancer patients.
Keloids and hypertrophic scars are abnormal responses to wound healing. In general, keloids exhib... more Keloids and hypertrophic scars are abnormal responses to wound healing. In general, keloids exhibit a proliferative growth beyond the margins of the scar and remain persistent; while hypertrophic scars are contained to the original wound and may regress over time. In particular, keloid formation is one of the most challenging clinical problems, with increasing frequency in surgical practice. Many treatments are available such as intralesional corticosteroids, topical applications, cryotherapy, surgical excision, radiation therapy, silicone gel sheeting, pressure therapy, and laser therapy. There are no set guidelines for the treatment of keloids and the most common treatments are individualized and depended on the distribution, size, thickness, and consistency of lesions. The authors have evaluated carbon dioxide laser successfully in the treatment of keloids and the aim of this study was to determine the immediate and long-term histologic and clinical effects of keloids after carbon dioxide laser. Fifty consecutive patients (40 females, 10 males, ages 18-60 years, mean age 40 years) with moderate to severe keloids were evaluated. All the patients received regional treatments (deltoid, elbow, chin, and ear) in an outpatient setting with a high-energy pulsed CO2 laser. Significant immediate and prolonged clinical improvement in skin tone, texture, and appearance of carbon dioxide laser was examined in all patients. Dermal remodeling was observed also on histologic examination of biopsied tissue after treatment. Carbon dioxide laser appears to be effective and well tolerated for the treatment of keloids, avoiding the adverse effects and lengthy recovery time.
The action of lateral habenula (LH) stimulation on focal epilcptiform activity in the hippocampus... more The action of lateral habenula (LH) stimulation on focal epilcptiform activity in the hippocampus was studied. Local microinjection of sodium penicillin induced a steady interictal activity in the dorsal hippocampus. Low frequency electrical stimulation of the habenula caused a marked enhancement of spike activity in both frequency and amplitude. The effect was blocked by intraperitoneally injected methyscrgide. The facilitatory influence of the habenula on hippocampal activity might be due to a disinhibitory mechanism. The results are regarded as suggesting that the habenula may be a relay station between the basal ganglia and the hippocampal formation. LH as well as basal ganglia might modulate hippocampal excitability, exerting a control on the genesis and diffusion of abnormal activities.
Substantia nigra is a mesencephalic structure inserted along several circuits which appear to pla... more Substantia nigra is a mesencephalic structure inserted along several circuits which appear to play a key role in epilepsy. In previous researches we postulated that substantia nigra pars compacta (SNpc) may be the site of a precise control of hippocampal epilepsy while substantia nigra pars reticulata (SNpr) may exert a modulation of both neocortical epilepsy and spreading of hyperactivity toward a motor target. In order to better understand mechanisms subserving nigral action in feline hippocampal epilepsy we electrically stimulated SNpc (dopaminergic), before and after sulpiride (dopamine receptor-antagonist) intravenous injection. Furthermore we compared hippocampal epileptiform activity prior to and after apomorphine (dopamine receptor-agonist) intrahippoeampal injection as well as prior to and after SNpc electrolytic destruction. Results showed that SNpc is able to regulate hippocampal epilepsy. This effect is selectively antagonized by sulpiride while apomorphine exerts, synergically with SNpc stimulation, inhibitory effects. On the contrary SNpc lesion induces a significant enhancement of hippocampal epileptiform spikes. Experimental findings suggest that SNpc represents a strategic region for the control of hippocampal excitability and that this regulation appears to be dopaminergic in nature.
Hippocampal-based epileptiform activity may reach the basal ganglia via the nucleus accumbens. Pr... more Hippocampal-based epileptiform activity may reach the basal ganglia via the nucleus accumbens. Previous data suggested that caudate nucleus is able to influence hippocampal epilepsy, probably sending a projection to the septum. In order to test the hypothesis of a retrograde activation of accumbens-caudate pathway in hippoc~pal regulation, we electrically stimulated both caudate rmcleus~ and nucleus accumbens and studied modifications of hippocampal EEG in the feline focal' epilepsy model. We also performed bilateral electrolytic lesion of nucleus accumbens and repeated caudate stimulation. Results showed that nucleus accumbens stimulation was ineffective in modifying hippocampal epilepsy ; on the contrary, caudate stimulation caused a statistically significant decrease of hippocampal spike fiequency and amplitude. On the other hand, in accumbens-lesioned animals caudate activation consistently reduced hi[?pocampal epilepsy to a s~gnificant degree. As the caudate nucleus influences hippocampal activity and the septum may constitute a relay station of this functional relation, a possibility was tested concerning a GABAergic mediation. To this end, after a stable caudate-induced effect was reached, an intraseptal microinjection of picrotoxin (GABA receptor antagonist) was made and caudate stimulation repeated at the same parameters. Such a study showed that after intraseptal picrotoxin, caudate stimulation failed to elicit any type of modification of hippocampal activity. Experimentat find'irtgs support the notion that the striatal modulation on hippocampus is mediated by an anterograde rather than a retrograde pathway, and underline the possibility of a GABAergic caudate-septal influence.
Previous experimental evidences showed that the caudate nucleus has a modulatory effect on hippoc... more Previous experimental evidences showed that the caudate nucleus has a modulatory effect on hippocampal epilepsy. The caudate's regulating action might reach the hippocampus either via the septal region or, retrogradely, via the accumbens nucleus. In order to obtain new data about the pathway involved in caudate hippocampal influence the spreading of abnormal activity towards the nucleus accumbens was studied. Furthermore the effects of caudate stimulation in animals with electrolytic lesions of the nucleus accumbens were analyzed. It was observed that abnormal penicillin-induced activity spreaded from the hippocampus to the nucleus accumbens in about 30 minutes. In animals with and without lesions of nucleus accumbens, caudate stimulation brought about a significant decrease in the frequency and amplitude of hippocampal activity. The results suggest that the nucleus accumbens is reached by the spreading of hippocampal epilepsy but does not participate in the control exerted by the caudate nucleus on the hippocampus. Thus the caudate-induced inhibition takes place through an anterograde caudate-hippocampal circuit, while at the same time excluding retrograde activation by way of a caudate-accumbens-hippocampal pathway.
Previous experimental investigations have shown that several neuronal systems modulate the sponta... more Previous experimental investigations have shown that several neuronal systems modulate the spontaneous and paroxysmal electric activity of the hippocampus. The locus coeruleus-noradrenaline (LC-NA) system exerts an inhibitory influence on several brain areas including the ipsilateral hippocampus. Selective destruction of the LC increases the susceptibility to epileptiform phenomena in different models of experimental epilepsy. Our experiments were conducted on 34 rats in which a steady epileptiform interictal activity of the hippocampus was obtained by means of intrahippocampal administration of penicillin. Electrical stimulation of LC caused a significant decrease of penicillin spiking of hip~ampus. Stimulation sessions given lo-15 min after i.p. propranolol administration (2 mg/kg) failed to induce any significant modification in the hippocampal spiking frequency. Intrahippocampal injection of L-noradrenaline mimicked the inhibitory effect of LC electrical stimulation on hip~c~p~.
Purpose: We investigated the role of nitric oxide (NO) a5 a new neurotransmitter in the control o... more Purpose: We investigated the role of nitric oxide (NO) a5 a new neurotransmitter in the control of excitability of the hippocampus and the cerebral cortex, as well as the possible functional interaction between NO and the glutamate systems. method,^: The experiments were performed on anesthetized rats. The bioelectrical activities of the somatosensory cortex and the CAI region of the hippocampus of these rats were recorded. Pharmacologic inhibition of NO synthase (NOS) through the nonselective and brain-selective inhibitors, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), was performed.
The current treatment of keloids is based on surgery, medical therapy and physical treatment. The... more The current treatment of keloids is based on surgery, medical therapy and physical treatment. The optimal treatment remains undefined. This clinical study determines the effectiveness of verapamil hydrochloride on the prevention and treatment of keloids. Two groups of patients with keloids were divided according to lesion site and age. The first group was treated by perilesional surgical excision of keloids and topical silicone, combined with adjuvant treatment of intralesional 2.5 mg/ml verapamil hydrochloride injections administered at timed intervals. The second group served as control, receiving the same treatment except the verapamil hydrochloride. A periodical examination to check specific clinical parameters and an 18-month follow-up determined that keloids were cured in 54% of the cases in the first group, compared to 18% in the second group. Moreover, in the remaining 36% of patients in the first group in whom keloids recurred, there was an improvement in size and above all in consistence. These findings suggest that verapamil hydrochloride is an effective tool for the prevention and therapy of keloids.
The mechanisms whereby the caudate nucleus modifies hippocampal spiking activity have been studie... more The mechanisms whereby the caudate nucleus modifies hippocampal spiking activity have been studied. Epileptiform activity was induced in the cat hippocampus by topical application of sodium penicillin in different concentrations. The frequency of induced spikes appeared to be directly correlated to the two doses of epileptogenic agent. The inhibitory effect of 10 Hz caudate stimulation on spike frequency was present even when stimulation lasted for 180 s. Likewise 25 Hz caudate stimulation brought about an inhibition which was maintained by stimulus trains lasting up to 90 s, while the degree of inhibition was reduced by trains of longer duration (120, 150 and 180 s); similar results were also noted in some atropine-treated cats. The time course of spikes in cats with electrolytic lesions of the caudate exhibited an increase in both frequency and duration. The results indicate that there is an optimal parameter for caudate stimulation causing inhibition of penicillin-induced hippocampal spiking activity, and suggest the possibility of tonic control of hippocampal excitability exerted by the caudate nucleus.
During surgical procedures, coagulation complications may occur. Discriminating factors are multi... more During surgical procedures, coagulation complications may occur. Discriminating factors are multiple and may vary because of the anatomical regions involved and because of preexisting diseases. The aim of this study was to analyze changes in such hematological parameters of patients undergoing conventional abdominoplasty with standard surgical procedures under general anaesthesia. For the study, 40 patients (20 men and 20 women) 30 to 60 years with normal coagulation assessments, no previous or current history of hemorrhagic or thrombotic disease, and no primary family history of such problems were selected. All the patients underwent conventional abdominoplasty surgical procedures. Analysis of the results suggests that immediately after surgery, in the absence of any preexisting hypo-or hypercoagulability state, there was no circumstantial modification in coagulation factors considered predictive for thromboembolic risk. However, an interesting difference between male and female patients was noted. In the male group, there was an insignificant uniform downward trend of all values immediately after surgery.
Background: Human adult adipose tissue is an abundant source of mesenchymal stem cells (MSCs). Mo... more Background: Human adult adipose tissue is an abundant source of mesenchymal stem cells (MSCs). Moreover, it is an easily accessible site producing a considerable amount of stem cells.
Recent studies showed that mesenchymal stem cells derived from adipose tissue can promote tumour ... more Recent studies showed that mesenchymal stem cells derived from adipose tissue can promote tumour progression, raising some concerns regarding their use in regenerative medicine. In this context, we co-cultured either SAOS2 osteosarcoma or MCF7 breast cancer cells with human adipose stem cells (hASCs), in order to evaluate potential effects of cancer cells on hASCs differentiation, in vitro and in vivo. In this study we observed that both SAOS2 and MCF7 cell lines induced an increase in hASCs proliferation, compared to hASCs alone, but, surprisingly, neither changes in the expression of CD90, CD29, CD324 and vimentin, nor variations in the Twist and Slug mRNAs were detectable. Noteworthy, SAOS2 and MCF7 cells induced in hASCs an upregulation of CD34 expression and stemness genes, including OCT3/4, Nanog, Sox2 and leptin, and a decrease in angiogenic factors, including CD31, PDGFα, PDGFRα, PDGFRβ and VEGF. SMAD and pSMAD2/3 increased only in hASCs alone. After 21 days of co-culture, hASCs differentiated both in adipocytes and endothelial cells. Moreover, co-injection of MCF7 cells with hASCs led to the formation of a highly vascularized tumour. Taken together our findings suggest that mesenchymal stem cells, under tumour cell induction, do not differentiate in vitro or facilitate the angiogenesis of the tumour in vivo, thus opening interesting new scenarios in the relationship between cancer and stem cells. These findings may also lead to greater caution, when managing autologous fat grafts in cancer patients.
Keloids and hypertrophic scars are abnormal responses to wound healing. In general, keloids exhib... more Keloids and hypertrophic scars are abnormal responses to wound healing. In general, keloids exhibit a proliferative growth beyond the margins of the scar and remain persistent; while hypertrophic scars are contained to the original wound and may regress over time. In particular, keloid formation is one of the most challenging clinical problems, with increasing frequency in surgical practice. Many treatments are available such as intralesional corticosteroids, topical applications, cryotherapy, surgical excision, radiation therapy, silicone gel sheeting, pressure therapy, and laser therapy. There are no set guidelines for the treatment of keloids and the most common treatments are individualized and depended on the distribution, size, thickness, and consistency of lesions. The authors have evaluated carbon dioxide laser successfully in the treatment of keloids and the aim of this study was to determine the immediate and long-term histologic and clinical effects of keloids after carbon dioxide laser. Fifty consecutive patients (40 females, 10 males, ages 18-60 years, mean age 40 years) with moderate to severe keloids were evaluated. All the patients received regional treatments (deltoid, elbow, chin, and ear) in an outpatient setting with a high-energy pulsed CO2 laser. Significant immediate and prolonged clinical improvement in skin tone, texture, and appearance of carbon dioxide laser was examined in all patients. Dermal remodeling was observed also on histologic examination of biopsied tissue after treatment. Carbon dioxide laser appears to be effective and well tolerated for the treatment of keloids, avoiding the adverse effects and lengthy recovery time.
The action of lateral habenula (LH) stimulation on focal epilcptiform activity in the hippocampus... more The action of lateral habenula (LH) stimulation on focal epilcptiform activity in the hippocampus was studied. Local microinjection of sodium penicillin induced a steady interictal activity in the dorsal hippocampus. Low frequency electrical stimulation of the habenula caused a marked enhancement of spike activity in both frequency and amplitude. The effect was blocked by intraperitoneally injected methyscrgide. The facilitatory influence of the habenula on hippocampal activity might be due to a disinhibitory mechanism. The results are regarded as suggesting that the habenula may be a relay station between the basal ganglia and the hippocampal formation. LH as well as basal ganglia might modulate hippocampal excitability, exerting a control on the genesis and diffusion of abnormal activities.
Substantia nigra is a mesencephalic structure inserted along several circuits which appear to pla... more Substantia nigra is a mesencephalic structure inserted along several circuits which appear to play a key role in epilepsy. In previous researches we postulated that substantia nigra pars compacta (SNpc) may be the site of a precise control of hippocampal epilepsy while substantia nigra pars reticulata (SNpr) may exert a modulation of both neocortical epilepsy and spreading of hyperactivity toward a motor target. In order to better understand mechanisms subserving nigral action in feline hippocampal epilepsy we electrically stimulated SNpc (dopaminergic), before and after sulpiride (dopamine receptor-antagonist) intravenous injection. Furthermore we compared hippocampal epileptiform activity prior to and after apomorphine (dopamine receptor-agonist) intrahippoeampal injection as well as prior to and after SNpc electrolytic destruction. Results showed that SNpc is able to regulate hippocampal epilepsy. This effect is selectively antagonized by sulpiride while apomorphine exerts, synergically with SNpc stimulation, inhibitory effects. On the contrary SNpc lesion induces a significant enhancement of hippocampal epileptiform spikes. Experimental findings suggest that SNpc represents a strategic region for the control of hippocampal excitability and that this regulation appears to be dopaminergic in nature.
Hippocampal-based epileptiform activity may reach the basal ganglia via the nucleus accumbens. Pr... more Hippocampal-based epileptiform activity may reach the basal ganglia via the nucleus accumbens. Previous data suggested that caudate nucleus is able to influence hippocampal epilepsy, probably sending a projection to the septum. In order to test the hypothesis of a retrograde activation of accumbens-caudate pathway in hippoc~pal regulation, we electrically stimulated both caudate rmcleus~ and nucleus accumbens and studied modifications of hippocampal EEG in the feline focal' epilepsy model. We also performed bilateral electrolytic lesion of nucleus accumbens and repeated caudate stimulation. Results showed that nucleus accumbens stimulation was ineffective in modifying hippocampal epilepsy ; on the contrary, caudate stimulation caused a statistically significant decrease of hippocampal spike fiequency and amplitude. On the other hand, in accumbens-lesioned animals caudate activation consistently reduced hi[?pocampal epilepsy to a s~gnificant degree. As the caudate nucleus influences hippocampal activity and the septum may constitute a relay station of this functional relation, a possibility was tested concerning a GABAergic mediation. To this end, after a stable caudate-induced effect was reached, an intraseptal microinjection of picrotoxin (GABA receptor antagonist) was made and caudate stimulation repeated at the same parameters. Such a study showed that after intraseptal picrotoxin, caudate stimulation failed to elicit any type of modification of hippocampal activity. Experimentat find'irtgs support the notion that the striatal modulation on hippocampus is mediated by an anterograde rather than a retrograde pathway, and underline the possibility of a GABAergic caudate-septal influence.
Previous experimental evidences showed that the caudate nucleus has a modulatory effect on hippoc... more Previous experimental evidences showed that the caudate nucleus has a modulatory effect on hippocampal epilepsy. The caudate's regulating action might reach the hippocampus either via the septal region or, retrogradely, via the accumbens nucleus. In order to obtain new data about the pathway involved in caudate hippocampal influence the spreading of abnormal activity towards the nucleus accumbens was studied. Furthermore the effects of caudate stimulation in animals with electrolytic lesions of the nucleus accumbens were analyzed. It was observed that abnormal penicillin-induced activity spreaded from the hippocampus to the nucleus accumbens in about 30 minutes. In animals with and without lesions of nucleus accumbens, caudate stimulation brought about a significant decrease in the frequency and amplitude of hippocampal activity. The results suggest that the nucleus accumbens is reached by the spreading of hippocampal epilepsy but does not participate in the control exerted by the caudate nucleus on the hippocampus. Thus the caudate-induced inhibition takes place through an anterograde caudate-hippocampal circuit, while at the same time excluding retrograde activation by way of a caudate-accumbens-hippocampal pathway.
Previous experimental investigations have shown that several neuronal systems modulate the sponta... more Previous experimental investigations have shown that several neuronal systems modulate the spontaneous and paroxysmal electric activity of the hippocampus. The locus coeruleus-noradrenaline (LC-NA) system exerts an inhibitory influence on several brain areas including the ipsilateral hippocampus. Selective destruction of the LC increases the susceptibility to epileptiform phenomena in different models of experimental epilepsy. Our experiments were conducted on 34 rats in which a steady epileptiform interictal activity of the hippocampus was obtained by means of intrahippocampal administration of penicillin. Electrical stimulation of LC caused a significant decrease of penicillin spiking of hip~ampus. Stimulation sessions given lo-15 min after i.p. propranolol administration (2 mg/kg) failed to induce any significant modification in the hippocampal spiking frequency. Intrahippocampal injection of L-noradrenaline mimicked the inhibitory effect of LC electrical stimulation on hip~c~p~.
Purpose: We investigated the role of nitric oxide (NO) a5 a new neurotransmitter in the control o... more Purpose: We investigated the role of nitric oxide (NO) a5 a new neurotransmitter in the control of excitability of the hippocampus and the cerebral cortex, as well as the possible functional interaction between NO and the glutamate systems. method,^: The experiments were performed on anesthetized rats. The bioelectrical activities of the somatosensory cortex and the CAI region of the hippocampus of these rats were recorded. Pharmacologic inhibition of NO synthase (NOS) through the nonselective and brain-selective inhibitors, N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), was performed.
The current treatment of keloids is based on surgery, medical therapy and physical treatment. The... more The current treatment of keloids is based on surgery, medical therapy and physical treatment. The optimal treatment remains undefined. This clinical study determines the effectiveness of verapamil hydrochloride on the prevention and treatment of keloids. Two groups of patients with keloids were divided according to lesion site and age. The first group was treated by perilesional surgical excision of keloids and topical silicone, combined with adjuvant treatment of intralesional 2.5 mg/ml verapamil hydrochloride injections administered at timed intervals. The second group served as control, receiving the same treatment except the verapamil hydrochloride. A periodical examination to check specific clinical parameters and an 18-month follow-up determined that keloids were cured in 54% of the cases in the first group, compared to 18% in the second group. Moreover, in the remaining 36% of patients in the first group in whom keloids recurred, there was an improvement in size and above all in consistence. These findings suggest that verapamil hydrochloride is an effective tool for the prevention and therapy of keloids.
The mechanisms whereby the caudate nucleus modifies hippocampal spiking activity have been studie... more The mechanisms whereby the caudate nucleus modifies hippocampal spiking activity have been studied. Epileptiform activity was induced in the cat hippocampus by topical application of sodium penicillin in different concentrations. The frequency of induced spikes appeared to be directly correlated to the two doses of epileptogenic agent. The inhibitory effect of 10 Hz caudate stimulation on spike frequency was present even when stimulation lasted for 180 s. Likewise 25 Hz caudate stimulation brought about an inhibition which was maintained by stimulus trains lasting up to 90 s, while the degree of inhibition was reduced by trains of longer duration (120, 150 and 180 s); similar results were also noted in some atropine-treated cats. The time course of spikes in cats with electrolytic lesions of the caudate exhibited an increase in both frequency and duration. The results indicate that there is an optimal parameter for caudate stimulation causing inhibition of penicillin-induced hippocampal spiking activity, and suggest the possibility of tonic control of hippocampal excitability exerted by the caudate nucleus.
During surgical procedures, coagulation complications may occur. Discriminating factors are multi... more During surgical procedures, coagulation complications may occur. Discriminating factors are multiple and may vary because of the anatomical regions involved and because of preexisting diseases. The aim of this study was to analyze changes in such hematological parameters of patients undergoing conventional abdominoplasty with standard surgical procedures under general anaesthesia. For the study, 40 patients (20 men and 20 women) 30 to 60 years with normal coagulation assessments, no previous or current history of hemorrhagic or thrombotic disease, and no primary family history of such problems were selected. All the patients underwent conventional abdominoplasty surgical procedures. Analysis of the results suggests that immediately after surgery, in the absence of any preexisting hypo-or hypercoagulability state, there was no circumstantial modification in coagulation factors considered predictive for thromboembolic risk. However, an interesting difference between male and female patients was noted. In the male group, there was an insignificant uniform downward trend of all values immediately after surgery.
Background: Human adult adipose tissue is an abundant source of mesenchymal stem cells (MSCs). Mo... more Background: Human adult adipose tissue is an abundant source of mesenchymal stem cells (MSCs). Moreover, it is an easily accessible site producing a considerable amount of stem cells.
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Papers by G. Ferraro