Cr (VI) reduction by photocatalyic process: Nb2O5 an alternative catalyst.

In this study, Nb2O5 catalyst was applied in the photocatalytic process for the Chromium reduction. Cr (VI) is a compound classified as highly toxic and often found in industrial tannery effluents. The techniques used for the photocatalytic material characterization were: X-ray diffraction, Specific surface area (B.E.T method), photo-acoustic spectroscopy, Scanning Electron Microscopy (SEM) and X-ray Dispersive Energy Spectrometry (EDS). A comparison between Nb2O5 and TiO2 (widely used in photocatalytic reactions) indicated that Nb2O5 has 20% more Cr (VI) reduction than TiO2. Tests carried out with Nb2O5 calcined at 500 °C and with non-calcined Nb2O5 showed that the heat treatment did not favor the reaction. Parameters such as pH, radiation intensity, initial concentration of Cr (VI) and amount of catalyst were studied. The results indicated that the acid (pH 2), emitted radiation intensity (250 W), initial concentration Cr (VI) at 10 mg L-1 and 1.5 g L-1 Nb2O5 non-calcined are the process optimal conditions. In addition, the reuse tests for Nb2O5 in consecutive cycles four, were realized. Photostability was maintained at approximately 90% for all cycles when Nb2O5 calcined was used. On the other hand, when using Nb2O5 non-calcined reduced by 21% during the four tests. This behavior is possibly due to the greater adsorption capacity of the non-calcined material. Making the Nb2O5 catalyst attractive for considering larger scale tests.

Predictors and timing of recanalization in intracranial carotid artery and siphon dissection: an ultrasound follow-up study.

BACKGROUND: Intra- and extracranial internal carotid artery dissections (ICD) are two different pathological conditions. Extracranial dissection is considered to be among the most frequent causes of stroke in the young and the segment generally reopens in 2 out of 3 cases, completely or partially, within 6 months. Intracranial ICD (IICD) is considered a rare occurrence in stroke and, accordingly, there are few systematic published data. However, it is a clinically significant condition that may cause severely disabling ischemic stroke or subarachnoid hemorrhage. In the past, sole availability of invasive imaging methods for its detection may have induced an underreporting. The aim of the study was to analyze ultrasound findings, timing and predictors of recanalization in patients with IICD. METHODS: IICD acute patients admitted to our Stroke Unit were submitted to carotid sonographic seriated monitoring, daily for the 1st week after symptom onset, at day 14, at month 1 and every 3 months thereafter up to a follow-up of 4 years. Contrast carotid ultrasound was performed in patients with persistent occlusion after month 1. RESULTS: Fourteen acute patients with IICD were enrolled. Extracranial internal carotid patency was observed in 8 patients at first ultrasound scans; all of these showed complete intracranial recanalization within the 1st week and oral anticoagulants were withdrawn after 6 months. Conversely, in 6 patients retrograde extracranial internal carotid thrombosis was immediately observed, since the first ultrasound scans. In 4 of these the occlusion persisted after 4 years while 2 of them had only a partial recanalization, with evidence at contrast ultrasound of still late remodeling processes in the extracranial thrombus up to 2 years after the first observation; for this reason, in these 2 patients anticoagulation was not discontinued, while in the 4 patients with persistent, stable, occlusion, therapy was suspended 1 year after the diagnosis. CONCLUSIONS: Identification of the site of dissection - i.e. extra- versus intracranial - is fundamental in clinical studies for outcome and prognosis evaluation. Carotid ultrasound strict surveillance is important to monitor eventual recanalization in patients with ICD, even in a late phase. Retrograde internal carotid thrombosis seems to be correlated with persistent occlusion and partial recanalization. Remodeling of thrombotic material in the internal carotid artery may, however, continue for up to 2 years. In these cases, contrast ultrasound evidence of thrombus morphological changes may support the decision to continue anticoagulation.

Cardioembolic stroke: Protective effect of a severe internal carotid artery stenosis in a patient with cardiac embolism.

Cardioembolic stroke is generally caused by intracranial artery occlusion. Clots may be identified in the intracranial vessels by means of conventional neuroimaging in the acute phase. High-resolution ultrasonography may show some features suggestive of cardiac emboli when occluding extracranial carotid arteries. We describe a patient with cardioembolic ischemic stroke in the right hemisphere in whom a left internal carotid artery stenosis paradoxically protected the ipsilateral hemisphere from distal intracranial embolism. The patient also presented multiple acute ischemic embolic lesions in the right middle cerebral artery territory and in the right occipital lobe, which was fed by the posterior cerebral artery, anomally originating from the right carotid siphon. Interestingly, the left internal carotid artery--which showed a severe preexisting stenosis--was occluded by the cardiac clot, whereas the right internal carotid artery only presented a moderate stenosis that had probably allowed the clots to pass. Therefore, the severe left internal carotid artery stenosis may have blocked the cardiac embolus, preventing it from reaching the ipsilateral hemisphere.

Depression after minor stroke: prevalence and predictors.

BACKGROUND AND PURPOSE: Post-stroke depression (PSD) is one of the most frequent complications of stroke, with a prevalence ranging 20-60%. As PSD seems to be related to stroke severity, we hypothesized that the prevalence of PSD would be lower in patients with minor stroke. METHODS: We investigated the prevalence and predictors of PSD over a 30-month follow-up period in a cohort of patients with minor ischaemic stroke (NIHSS≤5). RESULTS: We enrolled 105 patients (mean age 64.38±11.2years, M/F 69/36). PSD was diagnosed in 43 (41%) patients, 40 (93%) of whom had dysthymia; 22% of patients were already depressed at 1month. The most frequent depressive symptoms (DSs) were working inhibition, indecisiveness, and fatigability. Patients who developed PSD were less educated (P=0.044) and diabetic (P=0.006). After excluding patients that were already depressed at 1month, we performed a logistic regression model to detect predictors of PSD. Crying (P=0.012, OR 1.067, CI 0.269-4.553) and guilt (P=0.007, OR 0.037, CI 0.02ì03-0.401) at baseline were two DSs found to be significantly correlated with PSD. Higher educational level (P=0.022, OR 0.084, CI 0.010-0.698) and diabetes (P=0.007, OR 14.361, CI 2.040-101.108) were the risk factors significantly correlated with PSD. CONCLUSION: Post-stroke depression is frequent even in patients with minor stroke. Early detection of DSs might help to predict long-term development of PSD. No correlation was observed between lesion site or side and the development of PSD.

Effects of a single mannitol bolus on cerebral hemodynamics in intracerebral hemorrhage: a transcranial Doppler study.

BACKGROUND: Mannitol infusion is widely used in clinical practice to reduce perilesional edema in intracerebral hemorrhage (ICH), though no controlled studies have yet provided evidence of its effects on clinical outcome or on cerebral blood flow impairment following the event. The aim of our study was to evaluate blood flow velocity changes in the middle cerebral arteries (MCA) after a mannitol bolus in patients with ICH. METHODS: Transcranial Doppler bilateral monitoring was performed for 90 min in 20 patients with ICH, during 100 ml mannitol bolus i.v. administration. The MCA mean flow velocities (MFVs) and pulsatility index (PI) were recorded. RESULTS: When the 'healthy' and the 'affected' hemispheres were compared, we observed higher MCA MFV and lower PI on the affected side than on the contralateral side, both at baseline and during the experiment. After the mannitol bolus, we observed a significant MFV increase, starting at the end of the infusion and lasting longer than 60 min in the MCA on the affected side alone. The PI increased after mannitol administration on the healthy side alone. CONCLUSIONS: A single bolus of mannitol modified cerebral hemodynamics in our patients with ICH, increasing flow velocities on the affected MCA. This effect may be a consequence of reduced edema in the perilesional areas. The increased PI on the unaffected side may be indicative of preserved pulsatility in the healthy hemisphere.

Serotonin toxicity: a short review of the literature and two case reports involving citalopram.

The serotonin toxicity (ST) is a potentially life-threatening adverse drug reaction results from therapeutic drug use, intentional self-poisoning, or inadvertent interactions between drugs. ST can be caused by a single or a combination of drugs with serotonergic activity due to excessive serotonergic agonism on central nervous system and peripheral serotonergic receptors (monoamine oxidase inhibitors, tricyclic antidepressants, SSRIs, opiate analgesics, over-the-counter cough medicines, antibiotics, weight-reduction agents, antiemetics, antimigraine agents, drugs of abuse, H2-antagonist and herbal products). The serotonin toxicity is often described as a clinical triad of mental-status changes (agitation and excitement with confusion), autonomic hyperactivity (diaphoresis, fever, tachycardia, and tachypnea), neuromuscular abnormalities (tremor, clonus, myoclonus, and hyperreflexia) and, in the advanced stage, spasticity; not all of these findings are consistently present. In this article, we describe two cases of ST due to interaction between Citalopram and two CYP2D6 inhibitors: Cimetidine and Topiramate and their clinical resolution after treatment discontinuation.

Advantages and pitfalls of three-dimensional ultrasound imaging of carotid bifurcation.

OBJECTIVES: Several specialists use three-dimensional (3D) ultrasound as adjuvant imaging technique in their clinical practice. It has been applied to study carotid plaque morphology, surface and volume during atherosclerosis progression. Nonetheless, no papers have so far described the use of this technique in conditions different than carotid stenosis, such as bifurcation anatomy changes of the caliber and vessel course modifications. METHODS: Patients admitted to our ultrasound laboratory for vascular screening were submitted to standard carotid duplex and to 3D ultrasound reconstruction of the carotid bifurcation. RESULTS: Forty normal subjects, 7 patients with caliber alterations (4 carotid bulb ectasia and 3 internal carotid lumen narrowing), 45 patients with course variations (tortuosities and kinking) and 35 patients with internal carotid artery stenosis of various degrees have been investigated. CONCLUSIONS: 3D ultrasound is a feasible technique. It can improve carotid axis imaging through a better presentation of caliber variations and vessel course 'at a glance'. 3D ultrasound from the inward flow can provide imaging of the stenosis, but stenosis quantification should always take into account the assessment of plaque morphology and vessel wall.

The London APP mutation (Val717Ile) associated with early shifting abilities and behavioral changes in two Italian families with early-onset Alzheimer's disease.

BACKGROUND/AIMS: Mutations in the amyloid precursor protein gene were the first to be recognized as a cause of Alzheimer's disease (AD). METHODS: We describe 2 Italian families showing the missense mutation in exon 17 of the amyloid precursor protein gene on chromosome 21 (Val717Ile), known as London mutation. RESULTS: In 1 family, this mutation was responsible for AD in 3 out of 7 siblings and it is also present in a fourth sibling who has only shown signs of executive dysfunction so far. Two subjects of the other family with AD diagnosis were carriers of the same mutation. CONCLUSION: All AD subjects showed a cognitive profile characterized by early impairment in long-term memory, shifting abilities and affective symptoms beginning in the fifth decade of life.

Neural basis of maternal communication and emotional expression processing during infant preverbal stage.

During the first year of life, exchanges and communication between a mother and her infant are exclusively preverbal and are based on the mother's ability to understand her infant's needs and feelings (i.e., empathy) and on imitation of the infant's facial expressions; this promotes a social dialog that influences the development of the infant self. Sixteen mothers underwent functional magnetic resonance imaging while observing and imitating faces of their own child and those of someone else's child. We found that the mirror neuron system, the insula and amygdala were more active during emotional expressions, that this circuit is engaged to a greater extent when interacting with one's own child, and that it is correlated with maternal reflective function (a measure of empathy). We also found, by comparing single emotions with each other, that joy expressions evoked a response mainly in right limbic and paralimbic areas; by contrast, ambiguous expressions elicited a response in left high order cognitive and motor areas, which might reflect cognitive effort.

Transcranial Doppler for brain death in infants: the role of the fontanelles.

OBJECTIVE: Transcranial Doppler (TCD) is a sensitive technique for circulatory arrest diagnosis in brain death when patterns such as reverberant flow and short systolic spikes are observed. In infants, the nonossified fontanelles compensate for intracranial hypertension. We describe TCD patterns in infants with brain death, different from adults, with the hemodynamic modifications induced by anterior fontanelle compression. METHOD: TCD was performed in 2 infants with diagnosed brain death admitted to the neonatal intensive care unit. RESULTS: TCD showed a large peak 'reverberant' flow, with a high peak systolic velocity and a consistent retrograde component, away from the brain. Compression of the anterior fontanelle induced, at first, a reduction in systolic flow with the subsequent appearance of the characteristic short systolic spikes. Upon compression removal, a brief increase in the systolic flow was observed before the prompt reappearance of the reverberant flow. CONCLUSION: TCD for brain death diagnosis should be done cautiously in infants. In these cases, reverberating flow may be indicative of circulatory arrest even if with a large peak and with a high peak systolic velocity. Heavy fontanelle compression may reproduce the classical adult TCD patterns of brain death, thus supporting the diagnosis of cerebral circulatory arrest.

Long-term effects of a sensitisation campaign on migraine: the Casilino study.

In 2003, we conducted a sensitisation campaign on migraine in the Casilino district of Rome, by sending a letter with the ID Migraine test to all the households and placing posters in the GPs' waiting room. Out of 195 headache patients recruited, 92% had migraine while 73% had never consulted a physician for headache. The aim of this study was to evaluate the long-term impact of this campaign. The follow-up was performed by a telephone interview. The questionnaire considered the characteristics of headache, quality of life, preventive and acute treatments, drug efficacy, comorbidity and subjective usefulness of the campaign. Of the 179 migraineurs, 90.5% (mean age 40.7 +/- 16.5, 139 females) were included in the follow-up. An improvement was observed in mean pain intensity (-13.9%; p < 0.0001) and mean HIT-6 score (-6.1%; p = 0.0003). The campaign was considered to be useful by 63.6% of cases, while 66.1% reported an improvement in their clinical status. Improved patients showed a decreased mean number of days with headache per month (-51.7%; p < 0.0001), pain intensity (-21.8%; p < 0.0001), headache duration (-18.1%; p = 0.0008)and HIT-6 score (-11.7%; p < 0.0001). Our data suggest that the effects of a "single shot" campaign are beneficial not only in a short-term perspective, but even in the longterm. Moreover, the lack of benefit in more severe cases suggests that such patients should not be treated by GPs alone: patients in whom the HIT-6 score, frequency,severity or duration of headache worsen should be promptly referred to the headache clinic.

Combined pharmacological and short-term psychodynamic psychotherapy for probable medication overuse headache: a pilot study.

We studied the effects of short-term psychodynamic psychotherapy (STPP) and pharmacological therapy in 26 consecutive patients with probable medication overuse headache (pMOH). Patients underwent a standard in-patient detoxification protocol, lasting a mean of 7 days. Eleven patients overused non-steroidal anti-inflammatory drugs (NSAIDs), five a combination of NSAIDs and triptans, four triptans, four a combination of NSAIDs, and three triptans and ergot derivates. Preventive therapy was initiated during detoxification. The STPP protocol comprised the Brief Psychodynamic Investigation (BPI) and psychoanalysis-inspired psychotherapy. All patients (groups A and B) underwent the BPI and pharmacological therapy. Half of the patients (group B) also not randomly underwent psychoanalysis-inspired psychotherapy. We found a significant interaction between time and group for headache frequency and medication intake. At 12-month follow-up, a statistically greater decrease in headache frequency and medication intake was observed in group B than in group A (P = 0.0108 and P = 0.0097, respectively). The relapse rate was much lower in group B patients at both 6 and 12 months [15.3%, odds ratio (OR) 0.11, P = 0.016, and 23%, OR 0.18, P = 0.047, respectively] than in group A. The risk of developing chronic migraine (CM) during follow-up was higher in group A than in group B at 6 (OR 2.0, P = 0.047) and 12 months (OR 2.75, P = 0.005). Our study suggests that STPP in conjunction with drug withdrawal and prophylactic pharmacotherapy relieves headache symptoms in pMOH, reducing both long-term relapses and the burden of CM.

Contrast carotid ultrasound for the detection of unstable plaques with neoangiogenesis: a pilot study.

OBJECTIVES: To evaluate whether contrast ultrasonography can be used to distinguish asymptomatic from symptomatic carotid plaques and provide insight into underlying pathophysiological differences. DESIGN: Contrast carotid ultrasound was performed in both symptomatic and asymptomatic patients referred for carotid endarterectomy. MATERIALS AND METHODS: Of 77 consecutive patients referred for carotid artery evaluation, 64 underwent carotid endarterectomy for asymptomatic cerebrovascular disease and 9 underwent urgent surgery for acute neurological deficits with hemiparesis. The endarterectomy specimens were assessed immunohistologically. RESULTS: In all 9 patients undergoing urgent surgery, contrast ultrasonography showed the accumulation of diffuse microbubble contrast at the base of the carotid plaque. This pattern was observed only in 1/64 of the patients undergoing surgery for asymptomatic carotid disease. Immunohistologically staining of the endarterectomy specimens showed that the area of microbubble contrast at the base of the symptomatic plaques was associated with an increased number of small diameter (20-30 microm) microvessels staining for vascular endothelial growth factor (VEGF). CONCLUSIONS: Contrast carotid ultrasonography may allow the identification of microvessels with neoangiogenesis at the base of carotid plaques, and differentiate symptomatic from asymptomatic plaques.

A descriptive study on constructional impairment in frontotemporal dementia and Alzheimer's disease.

BACKGROUND AND PURPOSE: Frontotemporal dementia (FTD) is a degenerative disorder characterized, in its frontal variant, by psychiatric onset, deficits in executive functions and sparing of memory and visuo-spatial abilities. Studies on visuo-spatial abilities in FTD and Alzheimer's disease (AD) have mainly focused on constructional abilities (CA) and have yielded contrasting data, often depending either on the task used or biases in the clinical selection of patients. The aim of our study was to evaluate the frequency of the CA impairment in FTD-fv and AD patients at the early stage of the disease, and to verify if some distinctive features of this impairment can characterize each pathology. METHODS: The copy-drawing task (Rey Complex Figure, RCF) of 41 patients with probable mild AD and 15 patients with probable mild FTD-fv were analysed by means of quantitative and qualitative indices. RESULTS: Data showed that both AD and FTD patients displayed similar RCF scores, as well as execution strategies, type of errors and global analysis. The FTD group only had a significant deficit in the analysis of inner details.

Alexithymia in multiple sclerosis: relationship with fatigue and depression.

OBJECTIVE: The aim of this study was to investigate the prevalence of alexithymia in a sample of patients with multiple sclerosis (MS) and to further evaluate the association between alexithymia and the occurrence of common disabling MS-related symptoms such as fatigue and depression. METHODS: Fifty-eight relapsing-remitting MS patients treated with interferon (IFN)-beta-1a underwent a complete neurological evaluation, including Expanded Disability Status Scale score assessment. Alexithymia, depressive symptoms and fatigue were assessed using the 20-item Toronto Alexithymia Scale, Beck Depression Inventory and Fatigue Severity Scale. RESULTS: Prevalence of alexithymia was 13.8%, with 27.6% of patients presenting borderline alexithymia. Sixty-seven per cent of the patients complained of fatigue while 29.3% of them were depressed. Higher levels of fatigue and depression were found in alexithymic patients when compared with non-alexithymic patients. Results from logistic regressions showed that alexithymia significantly contributes to the severity of fatigue and depression. CONCLUSIONS: Alexithymia was associated with increased severity of fatigue and depression.

Combined transcranial Doppler and EEG recording in vasovagal syncope.

BACKGROUND: In neurally mediated syncope a 'typical' EEG pattern during hyperventilation (HV) may be observed. This study aimed to investigate transcranial Doppler (TCD) and EEG variations in response to hyper- and hypocapnia using simultaneous recording. METHODS: Syncope patients with a typical EEG pattern during HV (SEEG+, n = 15) and those without abnormalities (SEEG-, n = 16) were compared with healthy controls (n = 20). Simultaneous TCD and EEG recordings were performed at rest (baseline), during 2 apnea tests and during HV. Cerebrovascular vasoreactivity, index for hypocapnia, total vasomotor reserve and time to flow velocity normalization after HV (t-norm) were recorded. RESULTS: With TCD, a reduction in Vasomotor reserve was observed in SEEG+ compared with the other 2 groups (control: 67 +/- 8%; SEEG-: 67 +/- 10%; SEEG+: 57 +/- 8%; p < 0.0001). t-norm was longer in all syncopal patients and in particular in SEEG+ (control: 20.2 +/- 3 s; SEEG-: 40 +/- 7 s; SEEG+: 123 +/- 45s; p < 0.0001). Quantitative EEG showed an increase in slow bands in all subjects during HV, small and nonsignificant in controls and SEEG-, higher and significant in SEEG+, related with flow reduction. CONCLUSIONS: Changes in the sympathetic modulation of cerebral vasoconstriction may explain both the pathophysiology of vasovagal syncope and the typical paroxysmal EEG findings.

Post-stroke depression.

Post-stroke depression (PSD) is the most frequent psychiatric complication of stroke. Its prevalence has been estimated to be around 30-35%, ranging from 20 to 60%. Despite the extensive literature on this topic, there is no agreement on causal mechanisms, risk factors and consequences of PSD. Stroke patients with PSD suffer higher mortality rates and show a minor improvement in rehabilitation programs in comparison to non depressed stroke patients. Consequently, they have worse functional outcomes and quality of life. The available evidence supports PSD as being multifactorial in origin, and consistent with the biopsychosocial model of mental illness. Nonetheless, the stroke itself poses the risk of depression. Stroke survivors are more predisposed to PSD compared to physically ill patients with similar levels of disability, even quite a long time after the stroke, regardless of other risk factors. Early effective treatment of depression may have a positive effect not only on depressive symptoms but also on the rehabilitation outcome of stroke patients. On the other hand, there is no definitive evidence that antidepressants or psychotherapy are useful to prevent depression. Implementing preventive and therapeutic strategies to reduce the risk of mood alteration and thus improve rehabilitation outcomes would appear important in the organization of stroke services.

Short-term evolution as a marker of vascular dementia versus Alzheimer's disease.

The diagnosis of vascular dementia (VaD) remains a controversial issue in many aspects and concepts. These nosologic problems are caused both by the methods, insufficient to ascertain the diagnosis, as well as by the weak consistency of the clinical concept of VaD itself. One of the most intriguing issues on VaD, and in particular on post-stroke dementia (PSD), is related to the time of development of cognitive decline. In clinical practice, the 3-month time threshold is usually chosen to enable resolution of a possible acute post-stroke delirium, and to obtain a more reliable cognitive assessment with a complete regression of acute neuropsychological stroke-related deficits. Another relevant issue is the possibility to predict which patient will develop PSD. In this regard, recent data indicate an overlap between Alzheimer's disease (AD) and PSD, which seems to share risk factors and neuropathology. In most population samples these two disorders appear together, and the consensus is growing that a degenerative component has a more important role in determining PSD onset shortly after stroke than previously recognized. Therefore, anamnestic data have a fundamental role in this prognostic approach.

Acute subcortical stroke and early serotonergic modification: a IDAP study.

The intensity dependence of the auditory-evoked potentials (IDAP) is inversely related to serotonergic tone. Depression is frequently observed after stroke, associated with cognitive impairment and increased mortality. Aim of this study was to investigate the serotonergic tone in acute stroke patients by IDAP. Consecutive patients with an acute stroke admitted in our stroke unit were evaluated using clinical and instrumental examinations and compared with healthy controls. The IDAP was calculated as the linear amplitude/stimulus intensity function (ASF) slope, by measuring the peak-to-peak amplitude of Nl-P2 on four blocks of different stimulus intensities. Twenty patients were enrolled; 11 had a right brain infarction; nine had depressive symptoms (DS). The ASF slope of the auditory-evoked potentials was markedly increased in stroke patients compared with controls (P = 0.021). Stroke patients with DS had a significant steeper ASF slope than controls (P = 0.017). There was no statistical difference in ASF slope between stroke patients without DS and controls. Post-stroke depression pathophysiology is still debated. Our study suggests that in acute stroke patients with DS, there is a direct involvement of the serotonergic system, regardless the degree of disability and the site of the lesion.

Limited nucleotide pools restrict Epstein-Barr virus-mediated B-cell immortalization.

Activation of cellular oncogenes as well as infection with tumor viruses can promote aberrant proliferation and activation of the host DNA damage response. Epstein-Barr virus (EBV) infection of primary human B cells induces a transient period of hyper-proliferation, but many of these infected cells succumb to an ataxia telangiectasia mutated/checkpoint kinase 2 (ATM/Chk2)-mediated senescence-like growth arrest. In this study, we assessed the role of DNA replicative stress and nucleotide pool levels in limiting EBV-infected B-cell outgrowth. We found that EBV triggered activation of the ataxia telangiectasia and Rad3-related (ATR) signaling pathway in the early rapidly proliferating cells, which were also significantly more sensitive to inhibition of the ATR pathway than late attenuated proliferating cells. Through nuclear halo assays, we determined that early EBV-infected cells displayed increased replicative stress and DNA damage relative to late proliferating cells. Finally, we found that early after infection, hyper-proliferating B cells exhibited limited deoxyribonucleotide triphosphate (dNTP) pools compared with late proliferating and EBV-immortalized lymphoblastoid cell lines with a specific loss of purine dNTPs. Importantly, supplementation with exogenous nucleosides before the period of hyper-proliferation markedly enhanced B-cell immortalization by EBV and rescued replicative stress. Together our results suggest that purine dNTP biosynthesis has a critical role in the early stages of EBV-mediated B-cell immortalization.